RESUMO
The physicochemical properties, pK(a), Log P and solubility of compound alpha, (5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazole), a new fasciolicide agent, were characterized using conventional methods. Also, its pharmacokinetics was evaluated in sheep and cattle. In both species an oral dose of 12 mg/kg was administered. Blood samples were collected during 144 h and analyzed by using an HPLC assay. Results showed that compound alpha is a weak base with a pK(a) value of 2.87 and log P of 1.44. The solubility was very low in aqueous solvents. Pharmacokinetic studies showed that in both species compound alpha could not be detected at any sampling time. The mean half-life (t(1/2)) values of alpha sulphoxide in sheep and cattle were 19.86 and 29.87 h, while the half-life values of alpha sulphone were 19.43 and 46.32 h respectively. C(max) values of alpha sulphoxide did not differ between species while alpha sulphone values were higher in cattle. Plasma protein binding of alpha sulphoxide was between 82% and 86%. These results, combined with the previous efficacy studies, suggest that compound alpha could be a promising fasciolicide agent.
Assuntos
Antiplatelmínticos/farmacocinética , Bovinos/metabolismo , Imidazóis/farmacocinética , Naftalenos/farmacocinética , Ovinos/metabolismo , Animais , Antiplatelmínticos/sangue , Antiplatelmínticos/farmacologia , Bovinos/sangue , Cromatografia Líquida de Alta Pressão/veterinária , Fasciolidae/efeitos dos fármacos , Feminino , Meia-Vida , Imidazóis/sangue , Imidazóis/farmacologia , Masculino , Naftalenos/sangue , Naftalenos/farmacologia , Óxidos/farmacologia , Ovinos/sangue , Compostos de Enxofre/farmacologia , Dióxido de Enxofre/farmacologiaRESUMO
The analysis of albendazole sulfoxide, albendazole sulfone, praziquantel and trans-4-hydroxypraziquantel in plasma was carried out by high-performance liquid chromatography-mass spectrometry ((LC-MS-MS). The plasma samples were prepared by liquid-liquid extraction using dichloromethane as extracting solvent. The partial HPLC resolution of drug and metabolites was obtained using a cyanopropyl column and a mobile phase consisting of methanol:water (3:7, v/v) plus 0.5% of acetic acid, at a flow rate of 1.0 mL/min. Multi reaction monitoring detection was performed by electrospray ionization in the positive ion mode, conferring additional selectivity to the method. Method validation showed relative standard deviation (precision) and relative errors (accuracy) lower than 15% for all analytes evaluated. The quantification limit was 5 ng/mL and the linear range was 5-2500 ng/mL for all analytes. The method was used for the determination of drug and metabolites in swine plasma samples and proved to be suitable for pharmacokinetic studies.
Assuntos
Albendazol/sangue , Anti-Helmínticos/sangue , Antiplatelmínticos/sangue , Praziquantel/sangue , Albendazol/análogos & derivados , Albendazol/farmacocinética , Animais , Anti-Helmínticos/farmacocinética , Antiplatelmínticos/farmacocinética , Biotransformação , Cromatografia Líquida de Alta Pressão , Indicadores e Reagentes , Praziquantel/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , SuínosRESUMO
In the present study we found that after a single oral dose of 1,800 mg of praziquantel, following a high-lipid diet and a high-carbohydrate diet, the maximum levels in plasma increased 243 and 515% and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271%, respectively.
Assuntos
Antiplatelmínticos/farmacocinética , Interações Alimento-Droga , Praziquantel/farmacocinética , Adulto , Antiplatelmínticos/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Dieta , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Meia-Vida , Humanos , Pessoa de Meia-Idade , Praziquantel/administração & dosagem , ComprimidosRESUMO
A direct enantioselective high-performance liquid chromatography method is described for the quantitative determination of praziquantel enantiomers in plasma samples. The method involves two-step extraction of plasma with toluene, evaporation of the solvent and chromatography on a Chiralcel OD-H column using hexane-ethanol (85:15, v/v) as the mobile phase and detection at 220 nm. The assay satisfies all of the criteria required for use in clinical pharmacokinetic studies.