Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Mais filtros

Medicinas Complementares
Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Drugs ; 77(3): 313-318, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28078644

RESUMO

BACKGROUND: Second-generation direct-acting antiviral agents are integral to treatment of hepatitis C (HCV) infection. Eight-week courses of ledipasvir/sofosbuvir (LDV/SOF) have been supported in some studies, but data are limited on efficacy in real-world use. Controversy exists regarding applicability of clinical trials to real-world effectiveness. We report virologic responses of patients with HCV genotype 1 infection receiving LDV/SOF for 8 or 12 weeks in a large integrated healthcare system. METHODS: All patients receiving LDV/SOF, without ribavirin, were identified from pharmacy records, and outcomes are reported. Only treatment-naïve patients without evidence of cirrhosis and hepatitis C viral load less than 6 million IU/ml were candidates for 8-week therapy. Treatment was at clinician discretion, but delivered by a multidisciplinary team and reviewed for appropriateness and adherence to these criteria by one of the authors, all experienced in hepatitis C treatment. Sustained viral response at 12 weeks (SVR 12) was contrasted between those receiving 8 and those receiving 12 weeks of treatment. RESULTS: Completed prescriptions for LDV/SOF, without ribavirin, as of 30 September 2015 were identified in 1021 patients. Five patients discontinued therapy due to medical reasons and 35 had incomplete follow-up viral load data, thus there were 981 evaluable patients: 377 treated for 8 weeks and 604 treated for 12 weeks. SVR 12 was virtually identical at 93.6 and 93.5%, respectively. Baseline characteristics differed between the two groups, as only treatment-naïve, non-cirrhotic, non-HIV-infected patients were eligible for an 8-week course of therapy. CONCLUSIONS: Eight-week courses of LDV/SOF are comparable to 12-week courses in real-world use among selected patients supported by a multidisciplinary team.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Prestação Integrada de Cuidados de Saúde , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Sofosbuvir/uso terapêutico , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Humanos , Sofosbuvir/administração & dosagem , Fatores de Tempo
2.
Basic Clin Pharmacol Toxicol ; 120(5): 457-465, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27883269

RESUMO

Artemether-lumefantrine (AL) is a first-line treatment for uncomplicated malaria. Absorption of lumefantrine (LUM) is fat dependent, and in children, intake is recommended with milk. We investigated whether oil-fortified maize porridge can be an alternative when milk is not available. In an open-label pharmacokinetic study, Ugandan children <5 years with uncomplicated Plasmodium falciparum malaria were randomized to receive standard six-dose AL treatment [one tablet (20 mgA/120 mg LUM) if <15 kg and two tablets if >15 kg] with milk (A) or maize porridge plus oil (B). Parametric two-sample t-test was used to compare relative oral LUM bioavailability. The primary end-point was LUM exposure till 8 hr after the first dose (AUC0-8 hr ). Secondary outcome included day 7 concentrations (d7LUM ), LUM exposure between days 7 and 28 (AUCd7-28 ) and day 28 PCR-adjusted parasitological response. Evaluable children (n = 33) included 16 in arm A and 17 in arm B. The AUC0-8 hr was comparable between A and B [geometric mean (95% CI): 6.01 (3.26-11.1) versus 6.26 (4.5-8.43) hr*µg/mL, p = 0.9]. Less interindividual variability in AUC0-8 hr was observed in B (p = 0.01), but d7LUM and AUCd7-28 were comparable. Children receiving two tablets had significantly higher exposure than those receiving one tablet [median d7LUM (505 versus 289 ng/mL, p = 0.02) and AUCd7-28 (108 versus 41 hr*µg/mL, p = 0.006)]. One parasitological failure (d28 recrudescence) was observed. Our findings suggest that oil-fortified maize porridge can be an alternative to milk in augmenting absorption of LUM. The lower LUM exposure observed in children dosed with one AL tablet needs further attention.


Assuntos
Antimaláricos/administração & dosagem , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Interações Alimento-Droga , Malária Falciparum/tratamento farmacológico , Administração Oral , Animais , Antimaláricos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Pré-Escolar , Etanolaminas/farmacocinética , Feminino , Fluorenos/farmacocinética , Humanos , Lactente , Lumefantrina , Masculino , Leite , Óleos de Plantas/administração & dosagem , Comprimidos , Fatores de Tempo , Resultado do Tratamento , Uganda , Zea mays
3.
Chemosphere ; 159: 565-569, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27343862

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) may affect biochemical and physiological processes in living organisms, thus impairing fitness related traits and influencing their populations. This imposes the need for providing early-warning signals of pollution. Our study aimed to examine changes in the activity of acetylcholinesterase (AChE) and the concentration of heat shock proteins (Hsp70) in homogenates of brain tissues of fifth instar gypsy moth (Lymantria dispar L.) larvae, exposed to the ubiquitous PAH, fluoranthene, supplemented to the rearing diet. Significantly increased activity of AChE in larvae fed on the diets with high fluoranthene concentrations suggests the necessity for elucidation of the role of AChE in these insects when exposed to PAH pollution. Significant induction of Hsp70 in gypsy moth larvae reared on the diets containing low fluoranthene concentrations, indicate that changes in the level of Hsp70 might be useful as an indicator of pollution in this widespread forest species.


Assuntos
Acetilcolinesterase/efeitos dos fármacos , Fluorenos/toxicidade , Proteínas de Choque Térmico HSP70/efeitos dos fármacos , Larva/química , Mariposas , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Química Encefálica/efeitos dos fármacos , Inibidores da Colinesterase , Dieta , Poluição Ambiental , Fluorenos/administração & dosagem , Larva/enzimologia , Roma (Grupo Étnico)
4.
World J Gastroenterol ; 21(37): 10598-603, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26457019

RESUMO

Many herbal medicines are effective anti-inflammatory agents and may therefore suppress the development of hepatocellular carcinoma (HCC). Recently, treatment with a single-tablet regimen containing ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with hepatitis C virus genotype 1 infection who did not respond to prior interferon-based treatment. Patients with chronic hepatitis C are expected to receive this treatment worldwide. However, many patients have hepatitis-like fatty liver and nonalcoholic steatohepatitis. A strategy to prevent the development of HCC in this subgroup of patients is urgently required. Whether herbal medicines can suppress the development of HCC remains to be established. However, herbal medicines are effective anti-inflammatory agents and may inhibit the development of HCC. Clinical trials exploring the effectiveness of herbal medicines in the prevention and treatment of HCC are therefore warranted. The current lack of knowledge and of educational programs is a barrier to increasing the use of potentially effective herbal medicines and performing prospective clinical trials.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Fitoterapia , Preparações de Plantas/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Benzimidazóis/administração & dosagem , Carcinoma Hepatocelular/prevenção & controle , Ensaios Clínicos como Assunto , Cisteína/uso terapêutico , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado Gorduroso/complicações , Fluorenos/administração & dosagem , Glicina/uso terapêutico , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/uso terapêutico , Ácido Glicirrízico/uso terapêutico , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/complicações , Sofosbuvir/administração & dosagem , Comprimidos
5.
Malar J ; 11: 184, 2012 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-22681769

RESUMO

BACKGROUND: The Lao Government changed the national policy for uncomplicated Plasmodium falciparum malaria from chloroquine to artemether-lumefantrine (AL) in 2005. Since then, no information on AL efficacy has been reported. With evidence of resistance to artemisinin derivatives in adjacent Cambodia, there has been a concern as to AL efficacy. Monitoring of AL efficacy would help the Lao Government to make decisions on appropriate malaria treatment. METHODS: The efficacy of a three-day, twice daily oral artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Xepon District, Savannakhet Province, southern Laos was studied over 42 days follow-up. This was part of a trial of thiamin supplementation in falciparum malaria. RESULTS: Of 630 patients with P. falciparum enrolled in the trial of thiamin treatment, 549 (87%, 357 children ≤15 years and 192 adults) were included in this study. The per protocol 42-day cure rates were 97% (524/541) [96% (337/352) for children and 99% (187/189) for adults, p = 0.042]. By conventional intention-to-treat analysis, the 42-day cure rates adjusted for re-infection, were 97% (532/549) [96% (342/357) in children and 99% (190/192) in adults, p = 0.042]. The proportion of patients who remained parasitaemic at day 1 after treatment was significantly higher in children [33% (116/356)] compared to adults [15% (28/192)] (p < 0.001) and only one adult patient had detectable parasitaemia on day 2. There were no serious adverse events. Potential side effects after treatment were reported more commonly in adults (32%) compared to children (15%) (p < 0.001). Patients with recrudescent infections were significantly younger, had longer mean time to fever clearance, and had longer median time to parasite clearance compared to those who were cured. CONCLUSIONS: The current nationally-recommended anti-malarial treatment (artemether-lumefantrine) remains highly efficacious for the treatment of uncomplicated falciparum malaria five years after introduction in Laos. Regular monitoring is required in case artemisinin-resistant P. falciparum parasites should appear. TRIAL REGISTRATION: ISRCTN85411059.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Malária Falciparum/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Combinação Arteméter e Lumefantrina , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Lactente , Laos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
6.
Malar J ; 11: 58, 2012 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-22369089

RESUMO

BACKGROUND: Drug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs. METHODS: A prospective single cohort study was conducted at Igombe health centre using artemether-lumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously. RESULTS: A total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/µl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites. CONCLUSION: The efficacy of artemether-lumefantrine for treatment of uncomplicated malaria is still high in the study area although the rate of re-infection is higher than previously reported. Parasite clearance after 48 hours was lower compared to previous studies. The prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study area while markers for SP resistance is still high. Artemether-lumefantrine may be selecting for wild type alleles on both positions (437 and 540) of pfdhps.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Resistência a Medicamentos , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Malária/tratamento farmacológico , Malária/epidemiologia , Antígenos de Protozoários/genética , Combinação Arteméter e Lumefantrina , Sangue/parasitologia , Pré-Escolar , Estudos de Coortes , Impressões Digitais de DNA , DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , Combinação de Medicamentos , Feminino , Seguimentos , Genótipo , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prevalência , Estudos Prospectivos , Tanzânia/epidemiologia , Resultado do Tratamento
7.
PLoS Med ; 8(11): e1001125, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22131908

RESUMO

BACKGROUND: It is uncertain to what extent oral supplementation with zinc can reduce episodes of malaria in endemic areas. Protection may depend on other nutrients. We measured the effect of supplementation with zinc and other nutrients on malaria rates. METHODS AND FINDINGS: In a 2×2 factorial trial, 612 rural Tanzanian children aged 6-60 months in an area with intense malaria transmission and with height-for-age z-score≤-1.5 SD were randomized to receive daily oral supplementation with either zinc alone (10 mg), multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Intervention group was indicated by colour code, but neither participants, researchers, nor field staff knew who received what intervention. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. The primary outcome, an episode of malaria, was assessed among children reported sick at a primary care clinic, and pre-defined as current Plasmodium infection with an inflammatory response, shown by axillary temperature ≥37.5°C or whole blood C-reactive protein concentration ≥ 8 mg/L. Nutritional indicators were assessed at baseline and at 251 days (median; 95% reference range: 191-296 days). In the primary intention-to-treat analysis, we adjusted for pre-specified baseline factors, using Cox regression models that accounted for multiple episodes per child. 592 children completed the study. The primary analysis included 1,572 malaria episodes during 526 child-years of observation (median follow-up: 331 days). Malaria incidence in groups receiving zinc, multi-nutrients without zinc, multi-nutrients with zinc and placebo was 2.89/child-year, 2.95/child-year, 3.26/child-year, and 2.87/child-year, respectively. There was no evidence that multi-nutrients influenced the effect of zinc (or vice versa). Neither zinc nor multi-nutrients influenced malaria rates (marginal analysis; adjusted HR, 95% CI: 1.04, 0.93-1.18 and 1.10, 0.97-1.24 respectively). The prevalence of zinc deficiency (plasma zinc concentration <9.9 µmol/L) was high at baseline (67% overall; 60% in those without inflammation) and strongly reduced by zinc supplementation. CONCLUSIONS: We found no evidence from this trial that zinc supplementation protected against malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00623857


Assuntos
Suplementos Nutricionais/efeitos adversos , Ferro/efeitos adversos , Malária Falciparum/tratamento farmacológico , Micronutrientes/uso terapêutico , Zinco/uso terapêutico , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Pré-Escolar , Suplementos Nutricionais/análise , Combinação de Medicamentos , Etanolaminas , Feminino , Fluorenos/administração & dosagem , Seguimentos , Humanos , Incidência , Lactente , Ferro/administração & dosagem , Ferro/uso terapêutico , Deficiências de Ferro , Malária/classificação , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/prevenção & controle , Malária Falciparum/classificação , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Masculino , Desnutrição/sangue , Desnutrição/epidemiologia , Micronutrientes/administração & dosagem , Micronutrientes/deficiência , Prevalência , Análise de Regressão , Tanzânia/epidemiologia , Zinco/administração & dosagem , Zinco/deficiência
8.
Am J Trop Med Hyg ; 82(4): 529-34, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20348494

RESUMO

A recent drug efficacy trial reported Coartem (artemether-lumefantrine) to be highly effective against Plasmodium falciparum in children less than 5 years of age in Papua New Guinea (PNG). In contrast, we have observed high levels of treatment failures in non-trial conditions in a longitudinal cohort study in the same age group in PNG. Recrudescences were confirmed by genotyping of three different marker genes to provide optimal discrimination power between parasite clones. After excluding genetic host factors by genotyping potentially relevant cytochrome P450 loci, the high number of treatment failures in our study is best explained by poor adherence to complex dosing regimens in combination with insufficient fat supplementation, which are both crucial parameters for the outcome of Coartem treatment. In contrast to the situation in classic drug trials with ideal treatment conditions, our field survey highlights potential problems with unsupervised usage of Coartem in routine clinical practice and under program conditions.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Animais , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Pré-Escolar , Estudos de Coortes , Gorduras na Dieta , Suplementos Nutricionais , Combinação de Medicamentos , Resistência a Medicamentos , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Regulação da Expressão Gênica , Genótipo , Humanos , Papua Nova Guiné/epidemiologia , Cooperação do Paciente , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
9.
Malar J ; 8 Suppl 1: S3, 2009 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-19818170

RESUMO

Artemisinin, from which the artemether component of Coartem (artemether/lumefantrine, AL) is derived, is obtained from the plant sweet wormwood (Artemisia annua) which has been used for over 2,000 years as a Chinese herbal remedy. Artemisinin was first identified by Chinese researchers as the active anti-malarial constituent of A. annua and its derivatives were found to be the most potent of all anti-malarial drugs. Artemether acts rapidly, reducing the infecting parasite biomass by approximately 10,000-fold per asexual life cycle. Lumefantrine, the other active constituent of AL, acts over a longer period to eliminate the residual 100-100,000 parasites that remain after artemether is cleared from the body and thus minimizes the risk of recrudescence. The two agents have different modes of action and act at different points in the parasite life cycle and show a synergistic action against Plasmodium falciparum in vitro. The combination of artemether and lumefantrine reduces the risk of resistance developing to either agent, and to date there are no reports of resistance to AL combined therapy in the malaria parasite that infects humans. Following a unique partnership agreement between Chinese authorities and Novartis, the manufacturer of AL, over 20 sponsored clinical studies have been undertaken in various malaria endemic regions and in travellers. These trials have involved more than 3,500 patients (including over 2,000 children), and led to identification of a six-dose, three-day regimen as the optimal dosing strategy for AL in uncomplicated falciparum malaria. AL has consistently shown 28-day polymerase chain (PCR)-corrected cure rates greater than 95% in the evaluable population, meeting WHO recommendations. More recently, Novartis and the Medicines for Malaria Venture have worked in partnership to develop Coartem Dispersible, a new formulation designed specifically to meet the specific needs of children with malaria. The dispersible tablets have shown similar high response rates to those observed with crushed standard tablets of AL. A partnership agreement between Novartis and WHO has seen over 250 million AL (Coartem) treatments (75% for children) being distributed to malaria patients in developing countries without profit, supported by training programmes and educational resources.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Ensaios Clínicos como Assunto , Esquema de Medicação , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Humanos , Plasmodium falciparum/efeitos dos fármacos
10.
Malar J ; 8 Suppl 1: S4, 2009 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-19818171

RESUMO

Artemether and lumefantrine (AL), the active constituents of Coartem exhibit complementary pharmacokinetic profiles. Artemether is absorbed quickly; peak concentrations of artemether and its main active metabolite, dihydroartemisinin (DHA) occur at approximately two hours post-dose, leading to a rapid reduction in asexual parasite mass and a prompt resolution of symptoms. Lumefantrine is absorbed and cleared more slowly (terminal elimination half-life 3-4 days in malaria patients), and accumulates with successive doses, acting to prevent recrudescence by destroying any residual parasites that remain after artemether and DHA have been cleared from the body. Food intake significantly enhances the bioavailability of both artemether and lumefantrine, an effect which is more apparent for the highly lipophilic lumefantrine. However, a meal with only a small amount of fat (1.6 g) is considered sufficient to achieve adequate exposure to lumefantrine. The pharmacokinetics of artemether or lumefantrine are similar in children, when dosed according to their body weight, compared with adults. No randomized study has compared the pharmacokinetics of either agent in pregnant versus non-pregnant women. Studies in healthy volunteers and in children with malaria have confirmed that the pharmacokinetic characteristics of crushed standard AL tablets and the newly-developed Coartem Dispersible tablet formulation are similar. Studies to date in healthy volunteers have not identified any clinically relevant drug-drug interactions; data relating to concomitant administration of HIV therapies are limited. While dose-response analyses are difficult to undertake because of the low rate of treatment failures under AL, it appears that artemether and DHA exposure impact on parasite clearance time while lumefantrine exposure is associated with cure rate, consistent with their respective modes of action. In conclusion, knowledge of the pharmacokinetic profiles of artemether and lumefantrine is increasing within a range of settings, including infants and children. However, additional data would be warranted to better characterize artemether and lumefantrine pharmacokinetics in patients with hepatic impairment, in pregnant women, and in patients undergoing HIV/AIDS chemotherapy.


Assuntos
Antimaláricos/farmacocinética , Artemisininas/farmacocinética , Etanolaminas/farmacocinética , Fluorenos/farmacocinética , Antimaláricos/administração & dosagem , Antimaláricos/sangue , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Artemisininas/sangue , Ensaios Clínicos como Assunto , Esquema de Medicação , Combinação de Medicamentos , Interações Medicamentosas , Etanolaminas/administração & dosagem , Etanolaminas/sangue , Fluorenos/administração & dosagem , Fluorenos/sangue , Humanos
11.
Int J Environ Res Public Health ; 5(1): 41-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18441404

RESUMO

The objective of this study was to evaluate how the vehicles of choice affect the pharmacokinetics of orally administered Fluoranthene [FLA] in rats. Fluoranthene is a member of the family of Polycyclic Aromatic Hydrocarbon chemicals. Fluoranthene exposure to humans may occur as a result of cigarette smoking, consumption of contaminated food and water, heating woods in stoves and boilers, industrial sources such as coal gasification, carbon and graphite electrode manufacturing. Adult male Fisher-344 rats were given single oral doses of 25 and 50 microg/kg FLA in tricaprylin, peanut oil, cod liver oil, Tween 80/isotonic saline (1:5) and 2% Alkamuls-EL620 through gavage. After administration, the rats were housed individually in metabolic cages and sacrificed at 2, 4, 6, 8, 10 and 12 hours post FLA exposure. Blood, lung, liver, small intestine, adipose tissue samples, urine, and feces were collected at each time point. Samples were subjected to a liquid-liquid extraction using methanol, chloroform, and water. The extracts were analyzed by a reverse-phase HPLC, equipped with a fluorescence detector. The results revealed a dose-dependent increase in FLA concentrations in plasma and tissues for all the vehicles used. Plasma and tissue FLA concentrations were greater for peanut oil; cod liver oil, and tricaprylin vehicles compared to Alkamuls (p < 0.05), and Tween 80/isotonic saline (1:5). Most of the FLA administered through peanut oil, cod liver oil and tricaprylin was cleared from the body by 8 hours (90%) and 12 hours (80%) post administration for the 25 microg/kg and 50 microg/kg dose groups, respectively. With both doses employed, the metabolism of FLA was highest when cod liver oil was used as a vehicle and lowest in vehicles containing detergent/water [cod liver oil > peanut oil > tricaprylin > alkamuls > Tween 80/isotonic saline (1:5)]. These findings suggest that uptake and elimination of FLA is accelerated when administered through oil-based vehicles. The low uptake of FLA from Alkamuls and Tween 80/isotonic saline may have been a result of the poor solubility of the chemical. In summary, our findings reiterate that absorption characteristics of FLA were governed by the dose as well as the dosing vehicle. The vehicle-dependent bioavailability of FLA suggests a need for the judicious selection of vehicles in evaluating oral toxicity studies for risk assessment purposes.


Assuntos
Fluorenos/química , Fluorenos/farmacocinética , Veículos Farmacêuticos/química , Veículos Farmacêuticos/farmacocinética , Absorção , Administração Oral , Animais , Área Sob a Curva , Caprilatos/química , Caprilatos/farmacocinética , Óleo de Fígado de Bacalhau/química , Óleo de Fígado de Bacalhau/farmacocinética , Meio Ambiente , Fluorenos/administração & dosagem , Fluorenos/sangue , Meia-Vida , Masculino , Óleo de Amendoim , Óleos de Plantas/química , Óleos de Plantas/farmacocinética , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Solubilidade , Distribuição Tecidual , Triglicerídeos/química , Triglicerídeos/farmacocinética
12.
Trop Med Int Health ; 13(1): 99-107, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18291008

RESUMO

OBJECTIVE: To describe the quality of outpatient paediatric malaria case-management approximately 4-6 months after artemether-lumefantrine (AL) replaced sulfadoxine-pyrimethamine (SP) as the nationally recommended first-line therapy in Kenya. METHODS: Cross-sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under-fives. RESULTS: We evaluated 193 facilities, 227 health workers and 1533 sick-child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in-service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight-specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker's cadre, in-service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing. CONCLUSIONS: Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost-effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin-based combination therapy in Africa.


Assuntos
Assistência Ambulatorial , Artemisininas/uso terapêutico , Fluorenos/uso terapêutico , Política de Saúde , Malária/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Pré-Escolar , Estudos Transversais , Combinação de Medicamentos , Etanolaminas , Fluorenos/administração & dosagem , Fidelidade a Diretrizes , Pessoal de Saúde , Humanos , Lactente , Recém-Nascido , Entrevistas como Assunto , Quênia , Padrões de Prática Médica , Avaliação de Programas e Projetos de Saúde , Sesquiterpenos/administração & dosagem
13.
Malar J ; 6: 92, 2007 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-17631681

RESUMO

BACKGROUND: A combination of artesunate (AS) plus sulphadoxine/pyrimethamine (SP) as first-line and artemether-lumefantrine (AL) as second-line treatment are currently recommended against uncomplicated P. falciparum infection in Sudan. However, there is limited information on the efficacy of ACTs in the country and only one report of PCR-corrected results for AS/SP only. METHODS: The WHO protocol for the assessment of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria was employed. Artesunate plus sulphadoxine/pyrimethamine (AS/SP) was compared to artemether-lumefantrine (AL) in a 28-day follow up. Samples that were classified as early treatment failure (ETF), late treatment failure (LCF) or late parasitological failure (LPF) were genotyped for msp-1 and msp-2 genes to differentiate recrudescence from reinfection. RESULTS: A total of 178 patients were screened and 160 met the enrollment criteria and were recruited to the study of which 157 (98.1%) completed the follow up and had an analysed treatment outcome. On the AS/SP arm, three (0.038%) patients were lost during the follow-up, two on day 1 and one on day 7, and 77 (96.3) completed the study, while all 80 (100%) patients completed the follow up in the AL arm. In the per protocol analysis for AS/SP the treatment outcome for patients who completed the follow-up were as follows: adequate clinical and parasitological response (ACPR); 84.4% ETF; 1.3%, LCF; 3.9%, (LPF); 10.4%. For the AL arm the out come was as follows, ACPR; 90%, ETF; 0%, LCF; 6.3% and LPF; 3.8%. However, when PCR-corrected, 6.5% (5/77) of patients treated with AS/SP maintained parasites from their primary infection, while (7/80) in the AL group maintained their initial parasite genotype. Therefore, PCR-corrected efficacy was 93.5% in the AS/SP treated group and for AL it was 91.3%. CONCLUSION: Both AS/SP and AL are highly effective for the treatment of uncomplicated falciparum malaria in eastern Sudan. However, AS/SP appears to have a slightly higher efficacy than AL, this may be due to patient compliance with the repeated dose rather than drug efficacy.


Assuntos
Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Adulto , Animais , Antígenos de Protozoários/genética , Antimaláricos/administração & dosagem , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Artesunato , Combinação de Medicamentos , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Feminino , Fluorenos/administração & dosagem , Fluorenos/uso terapêutico , Genótipo , Humanos , Malária/parasitologia , Masculino , Proteína 1 de Superfície de Merozoito/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Pirimetamina/administração & dosagem , Pirimetamina/uso terapêutico , Sesquiterpenos/administração & dosagem , Sesquiterpenos/uso terapêutico , Sudão , Sulfadoxina/administração & dosagem , Sulfadoxina/uso terapêutico , Resultado do Tratamento
14.
Malar J ; 6: 80, 2007 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-17570848

RESUMO

BACKGROUND: In view of the high level of chloroquine resistance in many countries, WHO has recommended the use of combination therapy with artemisinin derivatives in the treatment of uncomplicated malaria due to Plasmodium falciparum. Four antimalarial drug combinations, artesunate plus amodiaquine (Arsucam), artesunate plus mefloquine (Artequin), artemether plus lumefantrine (Coartem; four doses and six doses), and amodiaquine plus sulphadoxine-pyrimethamine, were studied in five health districts in Senegal. METHODS: This is a descriptive, analytical, open, randomized study to evaluate the efficacy and tolerability of these four antimalarial combinations in the treatment of uncomplicated falciparum malaria using the 2002 WHO protocol. RESULTS: All drug combinations demonstrated good efficacy. On day 28, all combinations resulted in an excellent clinical and parasitological response rate of 100% after correction for PCR results, except for the four-dose artemether-lumefantrine regimen (96.4%). Follow-up of approximately 10% of each treatment group on day 42 demonstrated an efficacy of 100%.The combinations were well tolerated clinically and biologically. No unexpected side-effect was observed and all side-effects disappeared at the end of treatment. No serious side-effect requiring premature termination of treatment was observed. CONCLUSION: The four combinations are effective and well-tolerated.


Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Adulto , Idoso , Amodiaquina/administração & dosagem , Amodiaquina/efeitos adversos , Amodiaquina/uso terapêutico , Animais , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Artemeter , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Artemisininas/uso terapêutico , Artesunato , Criança , Pré-Escolar , Combinação de Medicamentos , Resistência a Medicamentos , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Etanolaminas/efeitos adversos , Etanolaminas/uso terapêutico , Fluorenos/administração & dosagem , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Seguimentos , Humanos , Lactente , Lumefantrina , Mefloquina/administração & dosagem , Mefloquina/efeitos adversos , Mefloquina/uso terapêutico , Pessoa de Meia-Idade , Pirimetamina/administração & dosagem , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Senegal , Sesquiterpenos/administração & dosagem , Sesquiterpenos/efeitos adversos , Sesquiterpenos/uso terapêutico , Sulfadoxina/administração & dosagem , Sulfadoxina/efeitos adversos , Sulfadoxina/uso terapêutico , Resultado do Tratamento
15.
Trop Med Int Health ; 12(2): 195-200, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17300625

RESUMO

BACKGROUND: Artemether-lumefantrine (AL) is the only fixed, artemisinin-based combination antimalarial drug which is registered internationally and deployed on a large scale. Absorption of the hydrophobic lipophilic lumefantrine component varies widely between individuals and is greatly increased by fat coadministration; but patients with acute malaria are frequently nauseated and anorexic, making dietary advice difficult to comply with. The aim of this study was to describe the dose-response relationship between coadministration of fat and relative lumefantrine bioavailability, in order to determine the minimum amount of fat necessary to optimize absorption. METHOD: We conducted a multiple crossover pharmacokinetic study in 12 healthy volunteers. This compared the area under the plasma concentration-time curve (AUC) for lumefantrine after administration of a single dose of AL in the fasting state given with 0, 10, 40, 150 and 500 ml of soya milk corresponding to 0, 0.32, 1.28, 4.8 and 16 g of fat. All volumes of milk supplements were tested in all subjects with a 3- to 4-week washout period in-between. RESULTS: A dose-response relationship was demonstrated between the volume of soya milk administered and lumefantrine bioavailability. AL administration with soya milk increased the lumefantrine AUC more than five fold. The population mean estimated volume of soya milk required to obtain 90% of maximum effect (in terms of lumefantrine AUC) was 36 ml (corresponding to 1.2 g of fat). CONCLUSIONS: Coadministration of artemether-lumefantrine with a relatively small amount of fat (as soya milk) was required to ensure maximum absorption of lumefantrine in healthy adult volunteers.


Assuntos
Antimaláricos/farmacocinética , Etanolaminas/farmacocinética , Fluorenos/farmacocinética , Leite de Soja/administração & dosagem , Absorção , Administração Oral , Adulto , Antimaláricos/administração & dosagem , Área Sob a Curva , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Disponibilidade Biológica , Estudos Cross-Over , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Etanolaminas/administração & dosagem , Jejum , Feminino , Fluorenos/administração & dosagem , Interações Alimento-Droga , Humanos , Lumefantrina , Malária Falciparum/prevenção & controle , Masculino , Pessoa de Meia-Idade
16.
Malar J ; 5: 113, 2006 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-17125496

RESUMO

BACKGROUND: Presented here are the results of a comparative trial on the efficacy of three artemisinin-based combinations conducted from May to October 2004, in Pool Province, Republic of Congo. METHODS: The main outcome was the proportion of cases of true treatment success at day 28. Recrudescences were distinguished from re-infections by PCR analysis. A total of 298 children of 6-59 months were randomized to receive either artesunate + SP (AS+SP), artesunate + amodiaquine (AS+AQ) or artemether + lumefantrine (AL), of which 15 (5%) were lost to follow-up. RESULTS: After 28 days, there were 21/85 (25%) recurrent parasitaemias in the AS+SP group, 31/97 (32%) in the AS+AQ group and 13/100 (13%) in the AL group. The 28-day PCR-corrected cure rate was 90.1% [95% CI 80.7-95.9] for AS+SP, 98.5% [95% CI 92.0-100] for AS+AQ and 100% [95.8-100] for AL, thereby revealing a weaker response to AS+SP than to AL (p = 0.003) and to AS+AQ (p = 0.06). A potential bias was the fact that children treated with AL were slightly older and in better clinical condition, but logistic regression did not identify these as relevant factors. There was no significant difference between groups in fever and parasite clearance time, improvement of anaemia and gametocyte carriage at day 28. No serious adverse events were reported. CONCLUSION: Considering the higher efficacy of AL as compared to AS+SP and the relatively high proportion of cases with re-infections in the AS+AQ group, we conclude that AL is clinically more effective than AS+SP and AS+AQ in this area of the Republic of Congo. Implementation of the recently chosen new national first-line AS+AQ should be monitored closely.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Amodiaquina/administração & dosagem , Amodiaquina/uso terapêutico , Animais , Antimaláricos/administração & dosagem , Artemeter , Artemisininas/administração & dosagem , Artesunato , Pré-Escolar , República Democrática do Congo , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Feminino , Fluorenos/administração & dosagem , Fluorenos/uso terapêutico , Humanos , Lactente , Lumefantrina , Masculino , Sesquiterpenos/administração & dosagem , Sesquiterpenos/uso terapêutico , Resultado do Tratamento
17.
Malar J ; 5: 81, 2006 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-17020598

RESUMO

BACKGROUND: Artemisinin-containing therapies are highly effective against Plasmodium falciparum malaria. Insufficient numbers of tablets and inadequate package inserts result in sub-optimal dosing and possible treatment failure. This study reports the case of three, non-immune, expatriate workers with P. falciparum acquired in Africa, who failed to respond to artemisinin-based therapy. Sub-therapeutic dosing in accordance with the manufacturers' recommendations was the probable cause. METHOD: Manufacturers information and drug content included in twenty-five artemisinin-containing specialities were reviewed. RESULTS: A substantial number of manufacturers do not follow current WHO recommendations regarding treatment duration and doses. CONCLUSION: This study shows that drug packaging and their inserts should be improved.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Rotulagem de Medicamentos , Lactonas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Adulto , Antimaláricos/administração & dosagem , Artemeter , Artemisininas/administração & dosagem , Artesunato , Côte d'Ivoire , Relação Dose-Resposta a Droga , Rotulagem de Medicamentos/normas , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Feminino , Fluorenos/administração & dosagem , Fluorenos/uso terapêutico , Guias como Assunto , Guiné , Humanos , Lactonas/administração & dosagem , Lumefantrina , Parasitemia/tratamento farmacológico , Recidiva , Risco , Sesquiterpenos/administração & dosagem , Sudão , Suíça/etnologia , Falha de Tratamento , Organização Mundial da Saúde
18.
Acta Trop ; 100(1-2): 41-53, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17045558

RESUMO

To demonstrate the superiority of the six-dose over the four-dose regimen of artemether-lumefantrine (co-artemether, Coartem) in patients >12 years, data from 11 randomized clinical trials were pooled and analyzed. A total of 1368 patients with uncomplicated Plasmodium falciparum malaria (six-dose: 598; four-dose: 770) were included in the analysis, together with 717 patients treated with comparators. Analysis of the 28-day cure rate based on the ITT and evaluable populations yielded corrected cure rates for the six-dose regimen of 87% and 97% compared with 74% and 87%, respectively, with the four-dose regimen (P<0.0001, for both comparisons). For mefloquine/artesunate, the most frequently used comparator, cure rates were 87% and 99%, respectively. The six-dose regimen was well tolerated and not markedly different to the four-dose regimen. The main finding of our analysis is that the six-dose regimen of co-artemether is more effective than the four-dose regimen in adolescents and adults without compromising safety.


Assuntos
Antimaláricos , Artemisininas , Fluorenos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Sesquiterpenos , Adolescente , Adulto , Idoso , Animais , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Artemisininas/uso terapêutico , Combinação de Medicamentos , Etanolaminas , Feminino , Fluorenos/administração & dosagem , Fluorenos/efeitos adversos , Fluorenos/uso terapêutico , Humanos , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sesquiterpenos/administração & dosagem , Sesquiterpenos/efeitos adversos , Sesquiterpenos/uso terapêutico , Resultado do Tratamento
19.
Malar J ; 5: 65, 2006 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-16879742

RESUMO

BACKGROUND: In Sudan, chloroquine (CQ) remains the most frequently used drug for falciparum malaria for more than 40 years. The change to artemisinin-based combination therapy (ACT) was initiated in 2004 using the co-blister of artesunate + sulfadoxine/pyrimethamine (AS+SP) and artemether + lumefantrine (ART+LUM), as first- and second-line, respectively. This article describes the evidence-base, the process for policy change and it reflects the experience of one year implementation. Relevant published and unpublished documents were reviewed. Data and information obtained were compiled into a structured format. CASE DESCRIPTION: Sudan has used evidence to update its malaria treatment to ACTs. The country moved without interim period and proceeded with country-wide implementation instead of a phased introduction of the new policy. The involvement of care providers and key stakeholders in a form of a technical advisory committee is considered the key issue in the process. Development and distribution of guidelines, training of care providers, communication to the public and provision of drugs were given great consideration. To ensure presence of high quality drugs, a system for post-marketing drugs surveillance was established. Currently, ACTs are chargeable and chiefly available in urban areas. With the input from the Global Fund to fight AIDs, Tuberculosis and Malaria, AS+SP is now available free of charge in 10 states. CONCLUSION: Implementation of the new policy is affected by the limited availability of the drugs, their high cost and limited pre-qualified manufacturers. Substantial funding needs to be mobilized by all partners to increase patients' access for this life-saving intervention.


Assuntos
Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Cloroquina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Sesquiterpenos/uso terapêutico , Artemeter , Artesunato , Cloroquina/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Fluorenos/administração & dosagem , Fluorenos/uso terapêutico , Política de Saúde , Humanos , Lumefantrina , Malária Falciparum/epidemiologia , Vigilância de Produtos Comercializados , Pirimetamina/administração & dosagem , Pirimetamina/uso terapêutico , Sudão/epidemiologia , Sulfadoxina/administração & dosagem , Sulfadoxina/uso terapêutico , Fatores de Tempo
20.
Malar J ; 5: 43, 2006 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-16704735

RESUMO

BACKGROUND: The therapeutic efficacy of artesunate plus amodiaquine and artemether/lumefantrine were assessed in an area of Nigeria with high levels of Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine. PARTICIPANTS: Children aged 6 to 59 months with uncomplicated P. falciparum infection and parasite density 1,000 to 200,000 parasites/microL enrolled following informed consent by parents. METHODS: Eligible children were randomly assigned to receive either a 3-day course of artesunate (4 mg/kg) plus amodiaquine (10 mg/kg) or 6-dose course of artemether/lumefantrine (20/120 mg tablets) over three days. Patients were followed up with clinical and laboratory assessments until day 14 using standard WHO in-vivo antimalarial drug test protocol. RESULTS: A total 119 eligible children were enrolled but 111 completed the study. Adequate clinical and parasitological response (ACPR) was 47 (87.0%) and 47 (82.5%) for artemether-lumefantrine (AL) and artesunate+amodiaquine (AAMQ) respectively (OR 0.7, 95% confidence interval 0.22 to 2.22). Early treatment failure (ETF) occurred in one participant (1.8%) treated with AAQ but in none of those with AL. Two (3.7%) patients in the AL group and none in the AAQ group had late clinical failure. Late parasitological failure was observed in 9 (15.8) and 5 (9.3%) of patients treated with AAQ and AL respectively. None of participants had a serious adverse event. CONCLUSION: Artemether-lumenfantrine and artesunate plus amodiaquine have high and comparable cure rates and tolerability among under-five children in Calabar, Nigeria.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Amodiaquina/administração & dosagem , Animais , Antimaláricos/administração & dosagem , Artemeter , Artemisininas/administração & dosagem , Artesunato , Pré-Escolar , Combinação de Medicamentos , Resistência a Medicamentos , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Feminino , Fluorenos/administração & dosagem , Humanos , Lactente , Lumefantrina , Masculino , Nigéria , Plasmodium falciparum/efeitos dos fármacos , Sesquiterpenos/administração & dosagem , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA