RESUMO
The development and validation of a simple method for the simultaneous determination of ranitidine and metronidazole in human plasma is described. Plasma samples (250 microL) were deproteinized by precipitation with 60% perchloric acid, centrifuged and the supernatant directly injected into the HPLC. Separation was achieved in isocratic mode with a Shimpak C(18) column and a mobile phase consisting of 10mM potassium dihydrogen phosphate pH 3.5:acetonitrile (90:10, v/v) with UV detection at 315 nm. The method showed good selectivity and sensitivity. Good and consistent recovery for metronidazole and ranitidine was obtained: 96.22+/-3.52 and 95.00+/-4.50% for ranitidine (25-1000 ng/mL) and metronidazole (60-10,000 ng/mL), respectively (n=3). With this one-step sample preparation method, both ranitidine and metronidazole could be quantified simultaneously in human plasma with good precision (R.S.D.<15%) and accuracy (bias values below 15%). The limit of quantification for ranitidine and metronidazole were 20 and 40 ng/mL plasma, respectively.
Assuntos
Anti-Infecciosos/sangue , Antagonistas dos Receptores H2 da Histamina/sangue , Metronidazol/sangue , Ranitidina/sangue , Cromatografia Líquida de Alta Pressão , Etanol , Humanos , Indicadores e Reagentes , Percloratos , Padrões de Referência , Reprodutibilidade dos Testes , Hidróxido de Sódio , Solventes , Manejo de Espécimes , Sacarose , TemperaturaRESUMO
The aim of the present study was to develop a simple method to measure ranitidine, using 100 microL of plasma, by high-performance liquid chromatography with a Symmetry C(18) column and UV detection at 313 nm. Linearity was assessed in the range from 50 to 1500 ng ml(-1) and had a correlation coefficient of 0.999. The inter- and intra-day coefficients of variation were less than 7%. The limits of detection and quantitation were 5 and 15 ng ml(-1), respectively. Drug levels were determined satisfactorily in three patients. A simple and reliable method was developed which uses a microvolume of plasma, particularly useful in low-weight children.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Antagonistas dos Receptores H2 da Histamina/sangue , Ranitidina/sangue , Humanos , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta/métodosRESUMO
The plasmatic profiles of 12 healthy volunteers after oral administration of ranitidine (150 mg) were studied considering two compartmental models. We observed the presence of two peaks. The proposed mechanism responsible for the existence of secondary peaks includes enterohepatic recirculation and the existence of multiple sites of absorption along the gastrointestinal tract. For characterizing the pharmacokinetic aspect of the drug, both phenomena were described using two compartmental models. We calculated the pharmacokinetic parameters and statistical tests after fitting the data of each volunteer under both models proposed. Statistically significant differences were not found in the statistical test values but existed in the area under the curve (AUC) comparing between models. To decide which of the two proposed models gave the best approximation of the physiological phenomenon undergone, we studied the pharmacokinetic of the drug in the rat, an animal without gallbladder. After oral administration of ranitidine, the plasmatic profile of the animals showed at least two peaks. Less than 0.2% of an oral dose was recovered in bile as ranitidine. Therefore, and considering the rat has no post-absorptive depot from where the drug can be released discontinuously, enterohepatic recycling does not seem to contribute significantly to the occurrence of secondary peaks in the concentration-time profiles of rats. Considering the results, we proposed that the best model able to explain the plasmatic profiles found in man and rats after oral administration of ranitidine is the one that presents multiple sites of absorption along the gastrointestinal tract. It is important to define the correct model in the calculation of the AUC and so in the value of the absolute bioavailability.
Assuntos
Antiulcerosos/farmacocinética , Antagonistas dos Receptores H2 da Histamina/sangue , Antagonistas dos Receptores H2 da Histamina/farmacocinética , Ranitidina/farmacocinética , Adulto , Animais , Antiulcerosos/sangue , Área Sob a Curva , Bile/química , Bile/metabolismo , Disponibilidade Biológica , Biotransformação , Cromatografia Líquida de Alta Pressão , Humanos , Absorção Intestinal , Masculino , Modelos Biológicos , Ranitidina/sangue , Ratos , Ratos Wistar , Espectrofotometria UltravioletaRESUMO
The plasma and urine concentrations of famotidine, a new, potent H2-receptor antagonist, have been measured in 16 healthy young adults, 8 healthy elderly people and 18 patients with varying degrees of renal dysfunction after intravenous administration. Both the plasma elimination and renal excretion of famotidine were decreased in the elderly volunteers and renal patients. The renal clearance of famotidine averaged 4.43 ml/min/kg (310 ml/min) in normal young volunteers, which exceeded the mean creatinine clearance 1.55 ml/min/kg (109 ml/min), suggesting net secretion is a significant mechanism for elimination of famotidine. The ratio of famotidine renal clearance to creatinine clearance decreased as creatinine clearance decreased; these results suggest that the deterioration in the secretion process was much faster than that in glomerular filtration and are incompatible with the "intact nephron hypothesis". Nevertheless, both total body clearance and renal clearance were significantly correlated with creatinine clearance. The apparent half-life was also significantly correlated with creatinine clearance. Since famotidine is essentially free of dose-related adverse effects, dose adjustment in patients with mild renal insufficiency and in elderly people is not required; however, either a prolonged dosing interval or a decrease in daily dose during long-term therapy may be adapted for the patients with severe renal insufficiency to avoid accumulation and the potential undesirable effects.