RESUMO
The study aimed at finding effective techniques of qualitative and quantitative analysis of selected beta-adrenergic blockers, useful both for monitoring of therapy and for thanatological diagnosis of intoxications. The studies took advantage of gas chromatography (GLC) and high performance liquid chromatography (HPLC). For isolation of studied compounds from biological material, classical and solid phase extraction procedures (SPE) Extrelut-20 (Merck), Abselut Nexus (Varian), STRATA C--18 E (Phenomenex) were used. The program included the analysis of most frequently applied derivatives: Acebutolol, Atenolol, Bunitrolol, Bupranolol, Labetolol, Metipranolol, Metoprolol, Oxprenolol, Practolol, Propranolol.
Assuntos
Antagonistas Adrenérgicos beta/sangue , Antagonistas Adrenérgicos beta/isolamento & purificação , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Detecção do Abuso de Substâncias/métodos , Acebutolol/sangue , Atenolol/sangue , Bupranolol/sangue , Estudos de Avaliação como Assunto , Humanos , Labetalol/sangue , Metipranolol/sangue , Metoprolol/sangue , Oxprenolol/sangue , Practolol/sangue , Propanolaminas/sangue , Propranolol/sangue , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Bupranolol is a non-selective beta-adrenoceptor antagonist with a Ki-value of 6-15 nmol/l (equivalent to 1.5-4 ng/ml in plasma) at beta 1- (rat salivary gland) and beta 2-adrenoceptors (rat reticulocytes) in receptor binding studies with 3H-CGP 12177 in the presence of human plasma. After oral administration of 200 mg bupranolol to healthy volunteers, the maximal plasma concentration was observed within 1.2 h but it only reached a level close to the Ki-value. Elimination from plasma was rapid (t 1/2 = 2.0 h). Administration of 30 mg bupranolol in a transdermal delivery system (TTS) every 24 h to 6 healthy volunteers for 72 h yielded steady state plasma concentrations 4- to 5-times above the Ki-value as shown by in vitro inhibition of beta-adrenoceptor binding by plasma samples. The pharmacodynamic effect, measured as the reduction in exercise tachycardia, showed a stable inhibitory effect; antagonism of a bolus injection of isoprenaline indicated a 10- to 15-fold right shift of the dose-response curve during the observation period of 72 h. It is concluded that steady-state plasma concentrations and effect of the elsewise rapidly eliminated beta-blocker bupranolol can be achieved by a transdermal delivery system applied each day.
