Four subjects received 5 mg laC-glipizide orally and 3 subjects 1 mg intravenously. The average absorption of the oral dose was nearly 100% with peak plasma levels occurring between 90 and 360 min. The apparent half-life of plasma radioactivity was approximatively 3.7 h, the disappearance of radioactivity following complex kinetics due to metabolism of the drug. Extraction with CI-t2C12 and chromatography showed that in plasma 85% of the total radioactivity corresponded to unchanged glipizide, but in urine 98o/o to more polar and more readily excreted metabolites. The urinary excretion is 68% of t}le dose. The hypoglyeaemie effect of glipizide is comparable to glibenelamide. The administration of 14C-glipizide to two patients with renal insufficiency showed that the metabolism of the drug is independent of kidney function, that the rate of disappearance of the unchanged glipizide was approximately the same as in norreals, but that the "halflife" of the metabolites was increased to 20 h and more.
Bufuralol (Ro 3 - 4787, Angium) is a non selective beta-adrenoceptor blocking drug with some degree of sympathomimetic action and a longer duration of action than propranolol. Plasma concentrations of bufuralol and 1'-hydroxybufuralol, its main blood derivative which shows similar beta-adrenoceptor blocking properties, were determined in healthy volunteers after a 60 mg oral and a 20 mg intravenous dose. Peak plasma concentrations were higher for the parent drug but due to a longer elimination half-life, the metabolite concentrations became higher after a few hours (bufuralol t 1/2 = 2.7 +/- 0.9 h, metabolite t 1/2 = 6.1 +/- 1.5h). The bioavailability of the tablet tested was 46 +/- 15%. The occurrence of side-effects in a subject with abnormal pharmacokinetics of the drug in this study and in a previous study with this drug suggested the possibility of a pharmacogenetic anomaly. Determination of the plasma metabolic ratio in the family of this subject and in a larger population confirmed that aliphatic hydroxylation of bufuralol is under polymorphic control. Phenotyping of our volunteers with debrisoquine showed the present pharmacogenetic anomaly to be the same as the one reported for debrisoquine alicyclic hydroxylation. The occurrence of side-effects in poor metabolizers as seen with bufuralol illustrates the clinical relevance of the hydroxylation polymorphism. In Switzerland the frequency of poor metabolizers is about 9% as previously reported for caucasian British subjects.
The plasma concentrations of pindolol have been examined following the administration of single doses of 15 mg tablets to eight healthy male subjects. The apparent half-life of elimination in plasma (t1/2 = 4.05 h) and in urine (t1/2 = 3.21 h) was calculated using conventional pharmacokinetic methods. The renal clearance was estimated by plotting urinary excretion rates versus plasma concentrations; for all subjects these plots were curved. In addition to these graphical estimations, the plasma concentrations of pindolol and the urinary excretion data for each volunteer were simultaneously fitted using a one or two-compartment open body model; a computer program using non-linear regression algorithms was used. This procedure did not give an adequate fit to the data. Another type of data analysis, using a population - based model, permitted us to show that the renal elimination of pindolol in man comprises of two separate processes - tubular secretion and reabsorption, which was partially saturable under the experimental conditions. The theoretical relevance and clinical significance of these findings are discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.