RESUMO
A new high-performance liquid chromatography assay was developed for the determination of tenofovir, a nucleotide analogue, in plasma. A solid-liquid extraction procedure was coupled with a reversed-phase HPLC system. The system requires a mobile phase containing Na(2)HPO(4) buffer, tetrabutylammonium hydrogen sulfate and acetonitrile for different elution through a C(18) column with UV detection. The method proved to be accurate, precise and linear between 10 and 4000 ng/ml. The method was applied to determine trough levels of tenofovir in 11 HIV-infected patients with virologic failure under multiple antiretroviral therapy. This method was also successfully applied to a pharmacokinetic study in an HIV infected patient with renal failure.
Assuntos
Adenina/análogos & derivados , Adenina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Infecções por HIV/sangue , Organofosfonatos , Compostos Organofosforados/sangue , Inibidores da Transcriptase Reversa/sangue , Adenina/farmacocinética , Adenina/uso terapêutico , Monitoramento de Medicamentos , Infecções por HIV/tratamento farmacológico , Humanos , Compostos Organofosforados/farmacocinética , Compostos Organofosforados/uso terapêutico , Reprodutibilidade dos Testes , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/uso terapêutico , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta , TenofovirRESUMO
PURPOSE: The objective of this study was to investigate the pharmacokinetic/pharmacodynamic properties of an antiretroviral therapy in HIV-infected patients. METHOD: Eight HIV-infected patients received zidovudine, lamivudine, and indinavir as their first antiretroviral treatment. Pharmacokinetic data were analyzed separately using a one-compartmental model with first-order absorption, and the individual estimates were used to simulate drug concentrations. To determine the relationship between drug concentrations and the antiviral effect, an in vitro E(max) model was tested. Alternatively, a dynamic model was built describing the viral and cellular pathophysiology, including the turnover of viral replication in infected cells and the production of virus under treatment. RESULT: The E(max) model fit poorly the experimental data. The complex model was not identifiable with the data available in this study, however a simplified model allowed us to estimate the pharmacodynamic parameters reflecting the decrease of both infected cells and viral load under antiretroviral treatment. CONCLUSION: Using potent highly active antiretroviral therapy, the treatment was so effective that it was not possible to estimate the parameters of the relationship between drug concentrations and the reduction of viral load. Even if the relationship does exist, the direct response model of antiretroviral agents cannot be demonstrated, however the simplified model provides an understanding of the synergy of such a combination and offers suggestions as how to prevent the emergence of viral resistant strains.
Assuntos
Fármacos Anti-HIV/farmacocinética , Modelos Biológicos , Adulto , Fármacos Anti-HIV/uso terapêutico , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , MasculinoRESUMO
BACKGROUND: The cosmetic use of bleaching products is considered a common practice in dark-skinned women from sub-Saharan Africa. However, there are few studies on this subject. OBJECTIVES: To increase the knowledge about the dermatological consequences of this practice in Dakar, the capital of Senegal. METHODS: A representative sample of 368 adult women presenting at our dermatological centre was selected. Each woman was questioned about her cosmetic use of bleaching products. Next, the following data were recorded in 425 women who used bleaching products: names and types of products used; modalities of the skin bleaching practice; skin diseases motivating the dermatological visit, with recording of their clinical features; and results of a full skin examination. The active substances of the bleaching products were determined mainly by reading the indications on their packages; with products of unknown composition, a pharmacological analysis of samples was done. A statistical analysis was performed. RESULTS: Of the 368 women questioned, 194 (52.7%) were current users of bleaching products. Concerning the 425 users enrolled, products were applied on the whole body in 92% of users, with a median duration of use of 4 years. The active principles used included hydroquinone (used by 89% of users), glucocorticoids (70%), mercury iodide (10%) and caustic agents (17%); 13% of users used products of unknown composition. In the samples that were analysed, hydroquinone was found at concentrations of between 4% and 8.7%. Concerning steroids, superpotent (class 1) glucocorticoids predominated. The main skin complaints in bleaching products users included dermatophyte infections (n = 105) and scabies (n = 69), both often unusually extensive and severe; acne (n = 42), often severe; eczema (n = 41); irritant dermatitis (n = 14); and dyschromia (n = 26, including 14 cases of exogenous ochronosis). The skin examination noted features apparently disregarded by users: striae (noticed in 39% of users), and macular hyperchromia involving the face, mainly the periocular area (33%). The statistical analysis showed that glucocorticoid use was associated with the presence and severity of infectious skin diseases, and of acne. CONCLUSIONS: More than half of the adult women presenting at our dermatology centre were using bleaching products. Most skin diseases observed in bleaching products users appeared to be induced, aggravated or modified by this practice. Superpotent topical glucocorticoids appeared to be the main agents responsible for the observed complications. The cosmetic use of bleaching products therefore has a major impact on our current dermatological practice.
Assuntos
Cosméticos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Dermatopatias/induzido quimicamente , Acne Vulgar/induzido quimicamente , Adolescente , Adulto , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Cáusticos/administração & dosagem , Cáusticos/efeitos adversos , Cosméticos/administração & dosagem , Cosméticos/química , Dermatite de Contato/etiologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/química , Dermatomicoses/induzido quimicamente , Eczema/induzido quimicamente , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidroquinonas/administração & dosagem , Hidroquinonas/efeitos adversos , Compostos de Mercúrio/administração & dosagem , Compostos de Mercúrio/efeitos adversos , Pessoa de Meia-Idade , Transtornos da Pigmentação/induzido quimicamente , Escabiose/induzido quimicamente , Senegal , Dermatopatias/patologiaRESUMO
Nefopam (NEF) and desmethyl-nefopam (DMN) were assayed simultaneously in plasma, globule and urine samples using imipramine as internal standard. A liquid-liquid extraction procedure was coupled with a reverse phase high-performance liquid chromatography system. This system requires a mobile phase containing buffer (15 mM KH(2)PO(4) with 5 mM octane sulfonic acid: pH 3.7) and acetonitrile (77:33, v/v) through (flow rate=1.5 ml/min) a C(18) Symmetry column (150x4.6 I.D., 5 micrometer particle size: Waters) and a UV detector set at 210 nm. Internal standard was added to 1 ml of plasma or globule sample or 0.5 ml of urine sample, prior to the extraction under alkaline ambiance with n-hexane. The limits of quantification were 1 and 2 ng/ml for both molecules in plasma and globule, respectively; 5 and 10 ng/ml for NEF and DMN in urine, respectively. The method proved to be accurate and precise: the relative error at three concentrations ranged from -13.0 to +12.3% of the nominal concentration for all molecule and biological fluid; the within-day and between-day precision (relative standard deviation %) ranged from 1.0 to 10.1% for all the molecules and biological fluids. The method was linear between 1 and 60 ng/ml for both molecules in the plasma; 2 and 25 ng/ml for both molecules in the globule; 25 and 250 ng/ml for NEF and 50 and 500 ng/ml for DMN in the urine: correlation coefficients of calibration curves (determined by least-squares regression) of each molecule were higher than 0.992 whatever the biological fluid and during the pre-study and in-study validations. This method was successfully applied to a bio-availability study of NEF in healthy subjects.
Assuntos
Nefopam/sangue , Nefopam/urina , Adulto , Área Sob a Curva , Cromatografia Líquida de Alta Pressão/métodos , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Nefopam/química , Nefopam/metabolismoRESUMO
A high-performance liquid chromatography (HPLC) procedure for the simultaneous determination of quinapril and its active metabolite quinaprilat in human plasma samples is described. A one-step solid-phase extraction (SPE) with C18 cartridges was coupled with a reversed-phase HPLC system. The system requires two mobile phases composed of tetrabutyl ammonium hydrogensulfate (10 mM adjusted to pH 7)-acetonitrile (62:38, v/v) for quinapril, and (25:75, v/v) for quinaprilat elution through a C18 Symmetry column and detection at a wavelength of 215 nm. Calibration curves were linear over the ranges 20 to 1,000 ng/ml for quinaprilat and 10 to 500 for quinapril. The limits of quantification were 20 and 10 ng/ml for quinaprilat and quinapril, respectively. Extraction recoveries were higher than 90% for quinapril and 80% for quinaprilat. This method has been successfully applied to a bioequivalence study of quinapril in healthy subjects.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Isoquinolinas/sangue , Espectrofotometria Ultravioleta/métodos , Tetra-Hidroisoquinolinas , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Calibragem , Humanos , Isoquinolinas/farmacocinética , Quinapril , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Equivalência TerapêuticaRESUMO
OBJECTIVE: To determine the cardiovascular, subjective effects and potential of abuse liability of single dose (-) ephedrine (E) administered orally (50 mg) or intranasally (10 mg and 5 mg). METHODS: Sixteen healthy Caucasian men with no history of drug/alcohol/nicotine abuse or dependence received intranasal single doses of E 5 mg, 10 mg and oral doses of 50 mg and placebo in a double-blind, double-dummy, crossover study. Dependent measures included assessment of subjective feelings by Addiction Research Centre Inventory (ARCI). Profile of Mood States (POMS). visual analogue scales (VAS); "drug liking", "any drug effect", subjective quality of sleep and blood pressure and heart rate. Plasma E concentrations were also determined. RESULTS: (-) E increased supine systolic, diastolic blood pressure (P < 0.01). Changes in supine systolic blood pressure (areas under the 8 h of the experimental sessions) were -59 +/- 47 mmHgh with placebo, -59 +/- 57 mmHg-h with E5 mg by the nasal route, -18 +/- 48 mmHg x h with E 10 mg by the nasal route and 13 +/- 58 mmHgh with E 50 mg by the oral route (P<0.001). (-) E-induced orthostatic hypotension (P < 0.01) (maximal systolic blood pressure drop: E 50 mg 14 +/- 10 mmHg, P < 0.03; E 10 mg 11 +/- 6 mmHg, P = 0.08 compared with placebo) and resulted in decreased tiredness (placebo -2 +/- 39 mm x h, E 5 mg -17 +/- 39 mm x h, E 10 mg -30 +/- 42 mm x h, E 50 mg -24 +/- 35 mm x h; P < 0.03). E did not modify ARCI subscales--in particular the "amphetamine" subscale--but showed a tendency for drug liking (P= 0.09). On the "any drug effect" questionnaire, subjects could identify drug effect (P=0.007). Maximal plasma E concentration (Cmax) and areas under the curves for up to 8 h were proportional to the doses. Elimination half-life was approximately 6 h. A clockwise hysteresis was observed for systolic blood pressure in all but one subject with E 50 mg by the oral route. CONCLUSION: E even at low doses and by the nasal route can decrease tiredness in healthy persons; this is accompanied by a substantial increase in blood pressure and orthostatic hypotension exposing individuals in case of intensive physical exercise to cardiovascular risks. No clear evidence of abuse liability in healthy drug naive subjects was observed.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacocinética , Efedrina/farmacocinética , Administração Intranasal , Administração Oral , Adulto , Área Sob a Curva , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/sangue , Estudos Cross-Over , Método Duplo-Cego , Efedrina/administração & dosagem , Efedrina/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Detecção do Abuso de Substâncias , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Abacavir is a potent, novel 2'-deoxyguanosine analogue reverse transcriptase inhibitor (NRTI) which effectively suppresses HIV-1 replication. To date, there is no pharmacokinetic study in patients with renal impairment. METHODS: Five HIV-1-infected patients with various degrees of renal dysfunction (creatinine clearance 60, 40, 25, 20 and 1 haemodialyzed patient) were evaluated after being treated for at least 2 months with multi-antiretroviral therapy including abacavir. After an overnight fast, the subjects received their abacavir dosage (600 or 300 mg). Blood samples were withdrawn and plasma concentrations determined. A nonparametric pharmacokinetic analysis was then performed. The dialysability of abacavir was also evaluated. RESULTS: Time of maximum plasma concentration (T(max)) was constant among the subjects with a mean value of 0.7 +/- 0.27 h (range 0.33-1). Maximum plasma concentration (C(max)) ranged from 2.76 to 4.15 mg/l (mean 3.44 +/- 0.59). The elimination half-life ranged from 1.31 to 2.67 h (mean 2.08 +/- 0.51). Normalized C(max)/dose ranged from 0.007 to 0.014 mg/l and normalized AUC(0-inf)/dose ranged from 0.014 to 0.035 mg.h/l. In haemodialysis the dialysance was 60-80 ml/min with a fractional drug removal of 24% during a 4-hour haemodialysis session with a high permeability membrane. DISCUSSION: In our patients, absorption, elimination and distribution phases were not altered by renal insufficiency. Furthermore, our pharmacokinetic data are similar to those obtained in patients with normal renal function. Therefore, dosage adjustment is not necessary in patients with renal insufficiency. In haemodialyzed patients, treatment can be administered independently to the dialysis session because of the negligible elimination of abacavir in the dialysate.
Assuntos
Fármacos Anti-HIV/farmacocinética , Didesoxinucleosídeos/farmacocinética , Infecções por HIV/tratamento farmacológico , HIV-1 , Insuficiência Renal/virologia , Administração Oral , Adulto , Fármacos Anti-HIV/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal/terapiaRESUMO
AIMS: Despite a lack of data, the antiviral agent ganciclovir is not indicated in AIDS patients with diarrhoea because of its presumed poor oral bioavailability. To assess the effect of diarrhoea on ganciclovir intestinal absorption, we conducted a pharmacokinetic study in 42 HIV-infected patients categorized into three groups: A, HIV stage A and B (n = 15); B, AIDS stage C (n = 13); C, AIDS with chronic diarrhoea and wasting syndrome (n = 14). METHODS: Each patient was evaluated for nutritional (body mass index, albumin, transferrin serum levels), inflammatory (haptoglobin, orosomucoid), immunological (CD4 count, plasma viral load) and intestinal (D-xylose test, faecal fat and nitrogen output, intestinal permeability) status. Ganciclovir (1 g) was administered orally to fasted patients. Six blood samples were collected over 24 h. Serum was analysed for ganciclovir by h.p.l.c. Population pharmacokinetic analysis was performed using a nonlinear mixed effects modelling program, MP2. RESULTS: Mean intestinal permeability (lactulose/mannitol urinary ratio) was increased in group C (0.2) compared with group A (0.05) and B (0.1) patients. Drug concentration-time profiles were best described by a two-compartment model. Apparent oral clearance (CL/F) and central volume of distribution (V1/F) were influenced by clinical status (group). For groups A and B combined, final parameter estimates of CL/F and V1/F were 256 +/- 98 l h(-1) and 1320 +/- 470 l, respectively. Final parameter estimates for group C were 118 +/- 108 l h(-1) and 652 +/- 573 l for CL/F and V1/F, respectively. The 95% confidence intervals on differences between A and B combined and C were statistically significant ([ + 70, + 206] for CL/F, and [+ 314, + 1022] for V1/F). Compared with groups A and B, ganciclovir CL/F was significantly decreased in group C patients. CONCLUSIONS: AIDS patients with diarrhoea and severe disease may benefit from ganciclovir therapy, but a dose adjustment may be required according to their digestive and immunological status.
Assuntos
Antivirais/farmacocinética , Diarreia/complicações , Ganciclovir/farmacocinética , Infecções por HIV/metabolismo , Síndrome de Emaciação por Infecção pelo HIV/complicações , Síndrome da Imunodeficiência Adquirida/metabolismo , Administração Oral , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/uso terapêutico , Infecções por HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/tratamento farmacológico , Síndrome de Emaciação por Infecção pelo HIV/metabolismo , Humanos , Absorção Intestinal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estado Nutricional/efeitos dos fármacos , Permeabilidade , Fatores de Tempo , Redução de PesoRESUMO
Valacyclovir is an effective oral agent for the treatment of herpes virus infection, however, the pharmacokinetics of the drug are altered in renal failure. It is increasingly recognized that dose adjustment of oral valacyclovir in renal failure is necessary to avoid neurotoxicity. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) and immunocompromised patient. She developed neurotoxicity with an adjustment dosage of valacyclovir for a cutaneous zoster infection. The elimination half-time (15 h) was similar to that reported for end-stage renal disease patients, while the steady-state volume of distribution (85 l) and the area under the curve concentration (127 mg/l.h) were greater. The mean CAPD dialysance was only 5.27 ml/min with less than 1% of an administered dose being recovered in the 24-hour dialysate. 48 h after interrupting treatment, she recovered normal neurological status and 500 mg of valacyclovir every 2 days was effective and well tolerated.
Assuntos
Aciclovir/análogos & derivados , Aciclovir/farmacocinética , Aciclovir/toxicidade , Antivirais/toxicidade , Diálise Peritoneal Ambulatorial Contínua , Pró-Fármacos/farmacocinética , Pró-Fármacos/toxicidade , Valina/análogos & derivados , Valina/farmacocinética , Valina/toxicidade , Antivirais/farmacocinética , Feminino , Alucinações/induzido quimicamente , Herpes Zoster/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , ValaciclovirAssuntos
Nefropatia Associada a AIDS/sangue , Nefropatia Associada a AIDS/terapia , Inibidores da Protease de HIV/farmacocinética , Diálise Renal , Ritonavir/farmacocinética , Saquinavir/farmacocinética , Nefropatia Associada a AIDS/tratamento farmacológico , Inibidores da Protease de HIV/sangue , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Ritonavir/sangue , Saquinavir/sangueAssuntos
Fármacos Anti-HIV/farmacocinética , Nevirapina/farmacocinética , Diálise Renal , Inibidores da Transcriptase Reversa/farmacocinética , Adulto , Fármacos Anti-HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Nevirapina/sangue , Inibidores da Transcriptase Reversa/sangueRESUMO
OBJECTIVE: To determine whether diarrhea and intestinal malabsorption during HIV infection alter oral ganciclovir systemic exposure. METHODS: We studied the oral disposition of ganciclovir in 42 HIV-infected patients stratified into three groups: A (n = 15), HIV (stage A and B); B (n = 13), AIDS (stage C); and C (n = 14), AIDS with chronic diarrhea and wasting syndrome (10% or more weight loss). Each patient was evaluated for nutritional (body mass index, serum albumin and transferrin), immunologic (CD4 count, plasma viral load) and intestinal status (D-xylose test, fecal fat and nitrogen excretion, and intestinal permeability). Following an overnight fast, 1 g oral ganciclovir was given to patients. Six blood samples were collected over 24 hours. Serum was analyzed for ganciclovir by high performance liquid chromatography. Drug disposition was characterized using a population pharmacokinetic approach. RESULTS: Mean intestinal permeability increased as HIV disease progressed (0. 05, 0.1, and 0.2 for groups A, B, and C, respectively). Average weight-adjusted maximum concentration (Cmax) in group C was twofold more than that in group A and B patients (12.5 versus 6 and 6.4 ng/ml/kg), and average area under the curve (AUC0-infinity) was threefold greater in group C patients (193 versus 59 and 65 ng. hour/ml/kg in groups A and B, respectively). Mean oral clearance was threefold lower in group C (96 versus 258 and 212 L/hour in groups A and B, respectively). CONCLUSION: Because systemic exposure of oral ganciclovir is enhanced in AIDS patients with diarrhea and wasting syndrome, oral ganciclovir therapy may benefit these patients.
Assuntos
Antivirais/administração & dosagem , Antivirais/farmacocinética , Ganciclovir/administração & dosagem , Ganciclovir/farmacocinética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Administração Oral , Adulto , Antivirais/sangue , Disponibilidade Biológica , Contagem de Linfócito CD4 , Diarreia/complicações , Diarreia/metabolismo , Feminino , Ganciclovir/sangue , Infecções por HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/metabolismo , Humanos , Absorção Intestinal , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Permeabilidade , Redução de PesoRESUMO
A new high-performance liquid chromatography (HPLC) with UV detection assay was developed for the simultaneous determination of protease inhibitors (PIs), nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs, NNRTIs) using a single 1-ml plasma samples. A solid-liquid extraction procedure without internal standard was coupled with two separate reversed-phase HPLC systems; one for the determination of amprenavir, efavirenz, indinavir, nelfinavir, ritonavir, saquinavir (run time=32 min) and one for the determination of abacavir, didanosine, lamivudine, stavudine, nevirapine, zidovudine (run time=40 min). The first requires a mobile phase containing sodium phosphate buffer+ion pair-acetonitrile (50:50, v/v) through a C18 Symmetry column (250x4.6 mm I.D., 5 microm particle size), using variable wavelengths (241, 254 and 261 nm). The second system requires three mobile phases (potassium phosphate buffer+ion pair-acetonitrile) for different elution through a C18 Symmetry Shield column (250x4.6 mm I.D., 5 microm), using a single wavelength (260 nm). Peak-areas are linear; correlation coefficients are better than 0.998 for all compounds, with both inter- and intra-day relative standard deviations lower than 12%. Extraction recoveries are higher than 93% for PIs and NNRTIs and higher than 70% for NRTIs. The method is specific and sensitive and was used to determine trough and peak levels of antiretroviral drugs in HIV infected patients under various combinations of RTIs and PIs.
Assuntos
Fármacos Anti-HIV/sangue , Inibidores da Protease de HIV/sangue , Inibidores da Transcriptase Reversa/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria UltravioletaRESUMO
A high-performance liquid chromatography procedure for the determination of ephedrine and norephedrine using fluorimetric detection in plasma samples is described. A double liquid-liquid extraction was performed, followed by derivatization with 9-fluorenylmethyl chloroformate. The extracts were chromatographed with a 5-microm C18 (150x4.6 mm I.D.) column using a mobile phase composed of acetonitrile and water (52:48; v/v). The excitation and emission wavelengths were respectively 264 nm and 313 nm. Calibration curves were linear over the range 0 to 300 ng/ml for each analyte. The specificity of the method was demonstrated with several FMOC-reacting drugs. The limits of quantification are similar to those obtained with the reference method: 2 ng/ml for ephedrine and 5 ng/ml for norephedrine. This method has been successfully applied to the determination of ephedrine and norephedrine plasma levels after administration of low doses of ephedrine to healthy subjects.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Efedrina/sangue , Fluorenos/química , Fenilpropanolamina/sangue , Estabilidade de Medicamentos , Fluorometria/métodos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Simpatomiméticos/sangueRESUMO
We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the number of antiretroviral drugs taken by the patients. Proviral DNA was detected in approximately half of all samples of cervicovaginal secretions from HIV-1-infected women, regardless of the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the antiretroviral regimen. In cervicovaginal secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against protease and reverse-transcriptase pol genes were found. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.
Assuntos
Doenças dos Genitais Femininos/virologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adulto , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , DNA Viral/análise , DNA Viral/efeitos dos fármacos , DNA Viral/genética , Resistência Microbiana a Medicamentos , Feminino , Doenças dos Genitais Femininos/tratamento farmacológico , Genótipo , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/classificação , Humanos , Pessoa de Meia-Idade , Mutação , Filogenia , Provírus/efeitos dos fármacos , Provírus/genética , RNA Viral/análise , RNA Viral/efeitos dos fármacosAssuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Falência Renal Crônica/complicações , Diálise Renal , Inibidores da Transcriptase Reversa/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Quimioterapia Combinada , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Nevirapina/farmacocinética , Nevirapina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Saquinavir/farmacocinética , Saquinavir/uso terapêutico , Estavudina/farmacocinética , Estavudina/uso terapêuticoRESUMO
BACKGROUND: Oral anticoagulants and pulse high-dose intravenous methylprednisolone are often administered concomitantly, but no data on potential interactions are available. OBJECTIVE: To assess possible potentiation of oral anticoagulation by high-dose intravenous methylprednisolone. DESIGN: Prospective cohort study. SETTING: University hospital in Paris, France. PATIENTS: 10 consecutive patients concomitantly receiving methylprednisolone and oral anticoagulants (fluindione and acenocoumarol) and 5 consecutive controls receiving methylprednisolone alone. MEASUREMENTS: Serial determinations of the international normalized ratio (INR) and clotting factors during administration of pulse methylprednisolone. The total plasma fluindione concentration was determined in 3 patients. RESULTS: The mean INR was 2.75 (range, 2.02 to 3.81) at baseline and increased to 8.04 (range, 5.32 to 20.0) after methylprednisolone administration. Plasma fluindione concentrations and the INR increased after methylprednisolone administration. Methylprednisolone alone did not increase prothrombin time. CONCLUSIONS: The action of oral anticoagulants is potentiated by intravenous high-dose methylprednisolone. The INR should be monitored daily during concomitant administration of these medications.
Assuntos
Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Metilprednisolona/administração & dosagem , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Anticoagulantes/sangue , Fatores de Coagulação Sanguínea/metabolismo , Sinergismo Farmacológico , Feminino , Humanos , Infusões Intravenosas , Coeficiente Internacional Normatizado , Masculino , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Fenindiona/sangue , Estudos Prospectivos , Proteína C/metabolismo , Proteína S/metabolismo , Tempo de ProtrombinaAssuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/metabolismo , HIV-1 , Oxazinas/farmacocinética , Adulto , Alcinos , Benzoxazinas , Ciclopropanos , Monitoramento de Medicamentos , Infecções por HIV/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Diálise RenalRESUMO
Beraprost sodium (BPS), an orally active PGI2 (prostaglandine 12) analogue possesses vasodilatating and platelet aggregation inhibiting properties. It is being developed in peripheral arterial occlusive disease. As in future clinical practice BPS might be co-prescribed with oral anticoagulants, we investigated its interaction with fluindione, a vitamin K antagonist in healthy subjects in a randomised, double-blind, placebo-controlled, crossover study. Twelve healthy Caucasian male subjects randomly received BPS 40 microg t.i.d. or placebo for 3 days. There was a 7 day wash out between the two treatment periods. On day 3 of each treatment, the subjects ingested concomitantly a single oral dose of 20 mg of fluindione. The main assessment criterion was fluindione's pharmacokinetics. Secondarily, pharmacodynamic measurements of coagulation (prothrombin time, and International Normalised Ratio, INR) and platelet function (in vitro closure time assessed by PFA-100) were performed. Fluindione was assayed by HPLC with UV detection up to 96 h post-drug. No statistical difference could be evidenced on any fluindione pharmacokinetic parameters between BPS and placebo phases: t 1/2 (h): 35.9 (8.2) vs. 34.0 (4.2) [90% CI 105.8 (95.5-116.2)]; T(max) (h): 2.0 (0.5-6.0) vs. 4.0 (0.5-6.0) [90% CI 136.4 (70.7-208.9)]; Cmax (mg/L): 3.1 (0.6) vs. 2.9 (0.5) [90% CI 94.1 (85.8-103.2)]; AUC 0-inf (mg/h/L): 117.0 (31.5) vs. 113.9 (33.8) [90% CI 97.6 (87.5-108.8)]. The studied doses of BPS did not affect platelet function, at least as assessed by the in vitro platelet function testing. Twenty milligrams of fluindione marginally modified the PT ratio and INR, however, no statistically significant difference was found between BPS and placebo phases. In conclusion, a 3 day regimen of BPS 40 microg t.i.d. by oral route does not seem to affect pharmacokinetic parameters of a fluindione 20 mg single dose.