RESUMO
After a single oral dose of 30 or 60 mg of propantheline bromide peak plasma levels of the drug were reached within 2 h in six healthy men. Mean peak plasma concentrations were 20.6 and 53.1 ng/ml after 30 mg and 60 mg respectively. The mean apparent absorption and elimination half-lives after 30 mg dose were 0.22 and 1.57 h respectively, and similar half-lives were found at the higher dose level. There was a dose related change in plasma levels and AUCinfinity of the drug, and some 3% to 4% of the administered dose of propantheline bromide was excreted unchanged in urine at each dose level. Comparison of the plasma levels and urinary excretion of the drug with those seen after i.v. administration in an earlier study indicated an apparently low systemic availability of orally administered propantheline bromide. There was tentative evidence of a qualitative relationship between the oral dose administered, plasma concentrations and the effects of propantheline bromide on salivary excretion.
Assuntos
Propantelina/metabolismo , Administração Oral , Adulto , Meia-Vida , Humanos , Injeções Intravenosas , Absorção Intestinal , Cinética , Masculino , Propantelina/sangue , Propantelina/urina , Fatores de TempoRESUMO
The peak plasma concn. of total radioactivity occurred 6 h after a single oral dose of [carboxyl-14C; methyl-2H3] propantheline bromide was administered to a healthy man. At this time 10% of the dose was present in the total plasma volume. 2. A total of 71% dose of radioactivity was excreted in urine in 96 h after dosage, 59% dose being excreted in the first 24 h. About 5.3% of the orally administered propantheline bromide was excreted unchanged. 3. T.l.c. analysis and g.l.c.-mass spectrometry showed xanthanoic acid, hydroxyxanthanoic acid(s), and propantheline as urinary metabolites of the drug. 4. A glucuronide of xanthanoic acid, a hydroxylated propantheline and the (2-hydroxyethyl)diisopropylammonium ion were tentatively identified as urinary metabolites. Hydrolysis of propantheline and conjugation of the resulting xanthanoic acid appear to be the major routes of metabolism of this compound. 5. A mean elimination half-life of 9.2 h was obtained for the total radioactivity by pharmacokinetic analysis of plasma and urine levels of 14C.
Assuntos
Propantelina/urina , Adulto , Cromatografia Gasosa , Cromatografia em Camada Fina , Humanos , Cinética , Masculino , Espectrometria de Massas , Propantelina/sangueRESUMO
The measurement of propantheline ion has been accomplished in urine and plasma following administration of propantheline bromide to man. Trideuteropropantheline bromide is added to the biological fluid to act as a carrier and internal standard to quantify the propantheline ion using multiple ion monitoring. Methane was used as reactant gas but following the discovery of exchange of the trideuteromethyl group when using methane, ammonia was used for later analyses. The determination of propantheline ion in urine and plasma after administration of propantheline bromide to man is described.
Assuntos
Propantelina/análise , Deutério , Humanos , Marcação por Isótopo , Cinética , Métodos , Propantelina/sangue , Propantelina/urina , Fatores de TempoRESUMO
The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propanthelin and the structurally related compounds, diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by equilibrium dialysis and ultracentrifugation. The results show that BSA has a few binding sites (n less than 10) for the mentioned drugs. The association between the compounds under study and BSA are relatively weak. The binding constants are in the range of 10(3) l/Mol.
