PMID: 3772738Aug 1, 1986Paper

The impact of neglecting nonlinear plasma-protein binding on disopyramide bioavailability studies

Journal of Pharmacokinetics and Biopharmaceutics
R A Upton, R L Williams

Abstract

Disopyramide has nonlinear protein binding and thus the relationship between the extent of its bioavailability and AUC, the area under the plasma concentration-time curve, is nonlinear and absorption rate-dependent. The unbound species follows linear pharmacokinetics. A solution of disopyramide, the innovator's product, and two generic formulations were found to be statistically indistinguishable in their bioavailability of disopyramide, whether comparison was based upon AUC or area under the plasma unbound concentration-time curve (AUCu). The AUC and AUCu gave similar results because of truly similar bioavailability, coupled with sufficiently similar release rates, among the four preparations chosen for study. The concentration dependence of disopyramide protein binding and the time course of unbound plasma concentrations were fit by models which then allowed prediction of AUC under various biopharmaceutical scenarios. Nonlinear binding of disopyramide to plasma proteins renders AUC an insensitive parameter for the discrimination of products with different extents of bioavailability; immediate-release products allowing bioavailabilities of 75 or 125% relative to the solution can generate AUCs 86 and 112%, respectively, of that...Continue Reading

References

Feb 1, 1979·Journal of Pharmacokinetics and Biopharmaceutics·P J MeffinD C Harrison
Feb 1, 1978·Journal of Pharmacokinetics and Biopharmaceutics·K C Yeh, K C Kwan
Sep 1, 1978·British Journal of Clinical Pharmacology·D K DubetzJ H Tyrer
Jun 1, 1976·Journal of Pharmacokinetics and Biopharmaceutics·P H Hinderling, E R Garrett
Apr 1, 1985·Fertility and Sterility·J K Sherman, G W Jordan
Nov 1, 1974·Journal of Pharmaceutical Sciences·P H HinderlingE R Garrett
Dec 1, 1984·Journal of Pharmacokinetics and Biopharmaceutics·M ThibonnierR L Williams
Feb 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·K M GiacominiT F Blaschke
Jan 1, 1982·European Journal of Clinical Pharmacology·D B Haughey, J J Lima

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Citations

Jan 1, 1987·European Journal of Clinical Pharmacology·J BraunS Oie
Dec 21, 2004·British Journal of Clinical Pharmacology·Michi WakaumiAkio Fujimura
Jan 1, 1990·Fundamental & Clinical Pharmacology·J BarréJ P Tillement
Jun 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·S D HallG R Wilkinson

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