RESUMO
The pharmacokinetic study of a new original antipsychotic drug Dilept in healthy volunteers was performed. Volunteers received Dilept as single 20, 40 or 60 mg tablets. The parent drug in the human blood plasma was detected in low concentrations and short-term time due to intensive biotransformation with formation of two metabolites N-caproyl-L-prolyl-tyrosin (M-1) and N-caproyl-L-prolin (M-2). After 20 and 40 mg of Dilept parent drug was detected in certain time points and after 60 mg for 1 h. M-1 and M-2 metabolites were registered in the blood plasma for 4 - 8 h. Theirs concentrations were 10 - 100 times higher of unchanged drug ones. Metabolites pharmacokinetics in the studied dosage range was nonlinear.
Assuntos
Antipsicóticos/farmacocinética , Prolina/análogos & derivados , Tirosina/análogos & derivados , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Área Sob a Curva , Biotransformação , Esquema de Medicação , Humanos , Masculino , Prolina/administração & dosagem , Prolina/sangue , Prolina/farmacocinética , Comprimidos , Tirosina/administração & dosagem , Tirosina/sangue , Tirosina/farmacocinéticaRESUMO
There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability.
Assuntos
Antiulcerosos/farmacocinética , Úlcera Duodenal/tratamento farmacológico , Ácido Gástrico/metabolismo , Omeprazol/farmacocinética , Inibidores da Bomba de Prótons/farmacocinética , Adulto , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Disponibilidade Biológica , Úlcera Duodenal/metabolismo , Esomeprazol , Feminino , Determinação da Acidez Gástrica , Humanos , Masculino , Omeprazol/administração & dosagem , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Tempo , Distribuição TecidualAssuntos
Anti-Infecciosos/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Ácido Nalidíxico/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Varfarina/efeitos adversos , Idoso , Anti-Infecciosos/uso terapêutico , Anticoagulantes/uso terapêutico , Interações Medicamentosas , Hemorragia Gastrointestinal/diagnóstico , Humanos , Isquemia/cirurgia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/cirurgia , Masculino , Ácido Nalidíxico/uso terapêutico , Hemorragia Pós-Operatória/diagnóstico , Tromboembolia/prevenção & controle , Uretrite/complicações , Uretrite/tratamento farmacológico , Varfarina/uso terapêuticoRESUMO
The authors studied the duration of intragastric acid production at 20 mg of pariet in patients with hypergastric gastritis after determination of the individual type of parietal gastric cell reception. The study included 40 patients (12 women and 28 men aged 33.3 +/- 6.7 years). Predominant activity of H2 receptors was detected in 32 patients, while M-cholinoreceptor activity prevailed in six patients; in two patients receptor type was not defined. Latent period (3.1 +/- 0.5 hours), pH(max) (5.4 +/- 0.7), pH24h (3.5 +/- 0.4), pH(stimulated24h) (3.0 +/- 0.7) did not depend on the predominant sensitivity of either receptor type and was significantly higher in patients taking pariet than in patients receiving standard doses of omeprazole (2.2 +/- 0.5 h, 4.0 +/- 0.3, 2.4 +/- 0.3, and 1.2 +/- 0.3, respectively) or lansoprazole (2.2 +/- 0.6, 4.3 +/- 0.6, 2.6 +/- 0.3, and 1.3 +/- 0.3, respectively). The clinical effectiveness of pariet was evaluated in 20 patients (15 men and 5 women aged 51.6 +/- 5.4) after gastric resection, needing antisecretory therapy. Individual reception type was studied. The effects of pirenzepine and ranitidine (or famotidine) given in standard doses at the beginning of the week were studied in patients with predominant H2-hystaminergic, M-cholinergic, or unclear type. After that all patients received pariet 20 mg a day. None of the patients displayed predominant H2 receptor activity. In 14 patients predominant M-cholinoreceptor activity was noted; in six patients receptor type remained unclear. All the patients were administered ranitidine (or famotidine) during one week with no clinical effect. Six patients with unclear reception type were given gastrozepine for one more week, with no effect either. After the beginning of pariet 20 mg a day complaints disappeared in all patients within one or two days. The conclusion is that pariet in a standard dose possesses higher antisecretory effect vs. other proton pump inhibitors, unlike that of H2 histamine blockers, the latter not depending on the individual type of gastric parietal cell reception.