Integrated Pharmacokinetics and Pharmacodynamics of Atropine in Healthy Humans I: Pharmacokinetics

The pharmacokinetics of atropine in three healthy male volunteers after intravenous administration of 1.35 and 2.15mg of the drug was determined. Pharmacodynamic effects of atropine were measured simultaneously. All the data were fitted to a novel integrated kinetic–dynamic model. Plasma concentrati...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical sciences 1985-07, Vol.74 (7), p.703-710
Main Authors: Hinderling, Peter H., Gundert-Remy, Ursula, Schmidlin, Olga
Format: Article
Language:English
Subjects:
Adult
Atropine - metabolism
Atropine - pharmacology
Atropine - urine
Biotransformation
Humans
Injections, Intravenous
Kinetics
Liver - metabolism
Male
Tropanes - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The pharmacokinetics of atropine in three healthy male volunteers after intravenous administration of 1.35 and 2.15mg of the drug was determined. Pharmacodynamic effects of atropine were measured simultaneously. All the data were fitted to a novel integrated kinetic–dynamic model. Plasma concentrations of atropine and the amounts of atropine and its primary metabolite, tropine, excreted in the urine were measured by a sensitive gas chromatographic–mass spectrometric assay. The kinetics of elimination of atropine was first order. There was evidence that the kinetics of distribution of the drug was dose dependent. Two phases with apparent half-lives of 1 and 140min were distinguishable in accordance with a linear two-compartment disposition model for atropine. The urinary excretion of unchanged drug was 57% of the dose. The steady-state volume of distribution was 210L, implying extensive tissue binding and/or partitioning. Renal plasma clearance was 660mL/min, suggesting significant tubular secretion. The renal clearance of atropine depended on urine flow. Urinary excretion of tropine amounted to 29% of the dose. The kinetics of the metabolite was first order.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600740702