RESUMO
BACKGROUND: The following review is a compilation of the recent advances and knowledge on the behaviour of the most frequently used compounds to treat inflammatory bowel disease in an organism. RESULTS: It considers clinical aspects of each entity and the pharmacokinetic/pharmacodynamic relationship supported by the use of plasma monitoring, tissue concentrations, and certain aspects derived from pharmacogenetics.
Assuntos
Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Monitoramento de Medicamentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Farmacogenética , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: End-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. METHODS: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. KEY RESULTS: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. CONCLUSIONS AND INFERENCES: An ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.
Assuntos
Adaptação Psicológica , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/embriologia , Medidas de Resultados Relatados pelo Paciente , Adolescente , Adulto , Idoso , Comparação Transcultural , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The objectives of this randomized, double-blind study were to evaluate the pharmacokinetics, and the pharmacodynamic and gastrointestinal (GI) tolerance of cefditoren pivoxil in healthy adult male volunteers when it is administered three times a day. Twenty healthy volunteers were included in the study. On day 1, 10 subjects received a 200-mg single dose of cefditoren pivoxil and 10 received a 400-mg dose. After a washout period of 8 days, eight subjects received cefditoren pivoxil 400 mg b.i.d., eight received 400 mg t.i.d., and four received placebo for 10 days. Medication was taken 30 min after meals. Blood and urine collections were carried out on days 1, 9, 14 and 19. Volunteers were asked about any GI change, especially about bowel habits, nausea, vomiting and abdominal pain. The maximum cefditoren concentration (C(max)) had a mean value of 3.77+/-0.66 mg/l, and was reached between 1.5 and 3 h in the thrice-daily administration. In the twice-daily regimen, the C(max) was 3.27+/-0.64 mg/l. The mean time above breakpoint minumum inhibitory concentration (MIC), calculated with data from each pharmacokinetic profile, was always above 40%, in both the twice- and thrice-daily regimens. The half-life of cefditoren was 1.19+/-0.2 h and 1.36+/-0.2 h in the twice-daily and thrice-daily regimens, respectively. The C(max) of cefditoren in urine was reached between 2 and 4 h postadministration, with a mean value of 154.53 mg/l in the twice-daily regimen, and 186.59 mg/l in the thrice-daily administration. There were no differences between the groups in the incidence of GI adverse events. The present data show that the administration of cefditoren pivoxil 400 mg t.i.d. is possible because it is well tolerated, and it increases the probability of success when the MIC of the causative bacteria is close to the susceptibility breakpoint. The high concentrations of active drug in the urine enable cefditoren to be considered as a useful candidate for the treatment of uncomplicated urinary tract infections (UTIs).
Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Adolescente , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Área Sob a Curva , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Diarreia/induzido quimicamente , Método Duplo-Cego , Meia-Vida , Humanos , Masculino , Testes de Sensibilidade MicrobianaRESUMO
Organ transplantation has become one of the most important areas of medical research and, at present, is still the only therapeutical tool for several diseases. However, there are a number of factors related to transplantation, like immunosuppression and prolonged neutropenia that affect the incidence of infection. These infections are somehow peculiar to transplant recipients. In fact, there are infectious diseases that only occur in immunodepression situations and, moreover, clinical expression of these infectious diseases can be quite different from that in immunocompetent patients. Besides these aspects, some infections, due to the high prevalence described, must be considered for prevention strategies because they continue to be a principal cause of morbidity and mortality, either due to direct effects or to their implication in the pathogenesis of rejection. These strategies commence before transplantation by active immunization through vaccine administration to the patient and to people in the milieu and continue after transplantation with prophylaxis or pre-emptive therapy. The importance of infectious diseases in the evolution and prognosis of transplant recipients gives a special meaning to the understanding of associated infections, their clinical expression and ways of prevention and treatment.
Assuntos
Infecções/etiologia , Transplante de Órgãos , Transplante de Células-Tronco , Transplante de Coração , Transplante de Coração-Pulmão , Humanos , Imunocompetência , Hospedeiro Imunocomprometido , Infecções/tratamento farmacológico , Infecções/transmissão , Intestino Delgado/transplante , Transplante de Rim , Transplante de Pulmão , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/mortalidade , Transplante de Pâncreas , Fatores de Risco , Transplante de Células-Tronco/mortalidadeRESUMO
BACKGROUND: Consensus on standard methods to assess chronic abdominal pain in patients with irritable bowel syndrome (IBS) is currently lacking. AIM: To systematically review the literature with respect to instruments of measurement of chronic abdominal pain in IBS patients. METHODS: Systematic literature search was performed in PubMed/Medline databases for studies using pain measurement instruments in patients with IBS. RESULTS: One hundred and ten publications were reviewed. A multitude of different instruments is currently used to assess chronic abdominal pain in IBS patients. The single-item methods, e.g. the validated 10-point numeric rating scale (NRS), and questionnaires assessing gastrointestinal symptoms severity, focus mostly on the assessment of only the intensity of abdominal pain. Of these questionnaires, the validated IBS-Symptom Severity Scale includes the broadest measurement of pain-related aspects. General pain questionnaires and electronic momentary symptom assessment tools have been used to study abdominal pain in IBS patients, but have not yet been validated for this purpose. The evidence for the use of provocation tests, e.g. the rectal barostat with balloon distention, for measurement of abdominal pain in IBS is weak, due to the poor correlation between visceral pain thresholds assessed by provocation tests and abdominal pain as assessed by retrospective questionnaires. CONCLUSIONS: The multitude of different instruments to measure chronic abdominal pain in IBS makes it difficult to compare endpoints of published studies. There is need for validated instruments to assess chronic abdominal pain in IBS patients, that overcome the limitations of the currently available methods.
Assuntos
Dor Abdominal/diagnóstico , Dor Abdominal/psicologia , Síndrome do Intestino Irritável , Medição da Dor/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Dor VisceralRESUMO
Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. The CYP3A4/P-glycoprotein system is mainly localized in the liver and intestine. It is responsible for the severe first pass metabolism of sirolimus with a low bioavailability. Drugs like voriconazole, itraconazole, fluconazole, and erytrhomycin may decrease the metabolic activity of this enzymatic system. This report documents in five patients that coadministration of these antimicrobials with sirolimus increases the blood concentrations of the immunosuppressant. The dose-normalized trough blood concentration showed a mean increase of sevenfold with the coadministration of these drugs. It is essential to monitor the blood sirolimus concentrations and to adjust the sirolimus doses before and after coadministration of these drugs.
Assuntos
Antifúngicos/uso terapêutico , Transplante de Coração/fisiologia , Imunossupressores/uso terapêutico , Pirimidinas/uso terapêutico , Sirolimo/uso terapêutico , Triazóis/uso terapêutico , Idoso , Área Sob a Curva , Biotransformação , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Transplante de Coração/imunologia , Humanos , Imunossupressores/farmacocinética , Masculino , Sirolimo/farmacocinética , VoriconazolAssuntos
Anti-Inflamatórios não Esteroides , Cetorolaco , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Cetorolaco/farmacocinética , Cetorolaco/farmacologia , Cetorolaco/uso terapêuticoAssuntos
Ácidos Heptanoicos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipolipemiantes , Pirróis , Atorvastatina , Ensaios Clínicos como Assunto , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Ácidos Heptanoicos/efeitos adversos , Ácidos Heptanoicos/farmacologia , Ácidos Heptanoicos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Oxigenases de Função Mista/metabolismo , Pirróis/efeitos adversos , Pirróis/farmacologia , Pirróis/uso terapêuticoAssuntos
Diuréticos , Sulfonamidas , Animais , Diurese/efeitos dos fármacos , Diuréticos/efeitos adversos , Diuréticos/química , Diuréticos/farmacocinética , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Vias de Administração de Medicamentos , Avaliação de Medicamentos , Interações Medicamentosas , Edema/tratamento farmacológico , Humanos , Nefropatias/tratamento farmacológico , Estrutura Molecular , Natriurese/efeitos dos fármacos , Sulfonamidas/efeitos adversos , Sulfonamidas/química , Sulfonamidas/farmacocinética , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , TorasemidaAssuntos
Angiotensina II/antagonistas & inibidores , Anti-Hipertensivos/uso terapêutico , Losartan , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Ensaios Clínicos como Assunto , Interações Medicamentosas , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Inativação Metabólica , Recém-Nascido , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Losartan/efeitos adversos , Losartan/química , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Contração Miocárdica/efeitos dos fármacos , Natriurese/efeitos dos fármacos , Gravidez , SegurançaAssuntos
Anti-Infecciosos , Levofloxacino , Ofloxacino , Adolescente , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Bactérias/efeitos dos fármacos , Criança , Ensaios Clínicos como Assunto , Contraindicações , Resistência Microbiana a Medicamentos , Epilepsia/induzido quimicamente , Feminino , Humanos , Inativação Metabólica , Recém-Nascido , Masculino , Ofloxacino/efeitos adversos , Ofloxacino/farmacologia , Ofloxacino/uso terapêutico , Transtornos de Fotossensibilidade/induzido quimicamente , Gravidez , Distribuição TecidualAssuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Indanos/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Acetilcolina/fisiologia , Disponibilidade Biológica , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacocinética , Ensaios Clínicos como Assunto , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Donepezila , Interações Medicamentosas , Gastroenteropatias/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Inativação Metabólica , Indanos/efeitos adversos , Indanos/química , Indanos/farmacocinética , Oxigenases de Função Mista/metabolismo , Nootrópicos/efeitos adversos , Nootrópicos/química , Nootrópicos/farmacocinética , Piperidinas/efeitos adversos , Piperidinas/química , Piperidinas/farmacocinética , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distribuição TecidualRESUMO
It is well to assume that bioanalytical chromatographic methods for the determination of polar basic drugs are developed and optimised according to a standardised procedure which involves two alternatives: (a) modifications in the sample preparation procedures, and (b) changes in the stationary phase of the chromatographic system. In this paper, a simple and rapid chromatographic procedure using a specific analytical detection method (ESI tandem mass spectrophotometric detection) in combination with a fast and efficient sample work-up procedure, protein precipitation, is presented. A demonstration of the entire chromatographic procedure is given for an HPLC method for the determination of famotidine in human plasma, a basic polar drug with poor solubility in organic solvents. In order to optimize the mass detection of famotidine, several parameters such as ionization mode, fragmentor voltage, m/z ratios of ions monitored, type of organic modifier and eluent additive, were investigated. Each analysis required 5 min. The calibration curve of famotidine in the range 1-200 ng/ml was linear with a correlation coefficient of 0.9992 (n = 6), and a detection limit a signal-to-noise ratio of 3 was approximately 0.2 ng/ml. The within- and between-day variations in the famotidine analysis were 5.2 (n = 6) and 6.7% (n = 18), respectively. The applicability of this method was also demonstrated for the analysis of plasma samples in a Phase-I human pharmacokinetic study.