PMID: 6398364Dec 1, 1984Paper

Pharmacokinetic-pharmacodynamic analysis of unbound disopyramide directly measured in serial plasma samples in man

Journal of Pharmacokinetics and Biopharmaceutics
M ThibonnierR L Williams

Abstract

The pharmacokinetics and pharmacodynamics of the antiarrhythmic drug, disopyramide, were investigated in 12 volunteers who took 300 mg doses of 3 different capsule preparations and an aqueous oral solution of the drug at 1-week intervals. Concentrations of drug unbound to plasma proteins were measured by a sensitive immunoenzyme assay after ultrafiltration of plasma samples taken serially after dosing. QT interval was measured on serial ECG recordings with correction for changes in heart rate. Unbound concentrations of disopyramide were modelled by an open one-compartment pharmacokinetic model with a zero-order absorption rate and a lag time. There was no significant difference in parameter estimates between the four preparations, except for the lag time, which was significantly shorter for the solution preparation. The saturable protein binding of disopyramide was described by a hyperbolic model including a specific binding site and additional nonspecific binding. The pharmacodynamic relationship between unbound drug concentration and QT prolongation was fit by a simple linear model. This fit was better using unbound concentration of the drug than using total concentrations.

References

Sep 1, 1977·Clinical Pharmacokinetics·J L CunninghamD L Azarnoff
Feb 1, 1979·Journal of Pharmacokinetics and Biopharmaceutics·P J MeffinD C Harrison
Nov 1, 1978·British Journal of Clinical Pharmacology·S M BrysonJ R Lawrence
Jun 1, 1976·Journal of Pharmacokinetics and Biopharmaceutics·P H Hinderling, E R Garrett
Nov 1, 1974·Journal of Pharmaceutical Sciences·P H HinderlingE R Garrett
Oct 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·A KarimD L Azarnoff
Feb 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·K M GiacominiT F Blaschke
Jan 1, 1982·European Journal of Clinical Pharmacology·S M BrysonD J Sumner
Jun 1, 1980·British Journal of Clinical Pharmacology·B M DavidK F Ilett

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Citations

Jan 1, 1987·European Journal of Clinical Pharmacology·J BraunS Oie
Mar 21, 2001·Archives of Medical Research·J Pérez-UrizarG Castañeda-Hernández
Apr 1, 1990·British Journal of Clinical Pharmacology·H EchizenT Ishizaki
Jan 1, 1990·Fundamental & Clinical Pharmacology·N H Holford
Jan 1, 1990·Fundamental & Clinical Pharmacology·J BarréJ P Tillement
Nov 6, 1998·British Journal of Clinical Pharmacology·T J Campbell, K M Williams
Sep 1, 2006·Expert Opinion on Drug Discovery·Christian HöchtCarlos A Taira
Jan 1, 1989·Fundamental & Clinical Pharmacology·P CacoubC Jacobs
Dec 1, 1987·British Journal of Clinical Pharmacology·R P KapilC R Kerr
Feb 1, 1987·Journal of Pharmacokinetics and Biopharmaceutics·M YasuharaC Kawai
Aug 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·J P ReymondW Niederberger
Aug 1, 1986·Journal of Pharmacokinetics and Biopharmaceutics·R A Upton, R L Williams

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