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Penicillamine kinetics in normal subjects

R F Bergstrom, D R Kay, T M Harkcom

Clinical Pharmacology and Therapeutics

|September 1, 1981

Summary

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Penicillamine oral absorption shows unusual double peaks in plasma levels. Food intake significantly reduces penicillamine absorption, impacting its pharmacokinetic profile.

Area of Science:

Pharmacokinetics
Drug Metabolism

Background:

Penicillamine is an orally administered chelating agent.
Understanding its absorption and disposition is crucial for therapeutic efficacy.

Purpose of the Study:

To characterize the oral pharmacokinetics of penicillamine.
To investigate the effect of food on penicillamine absorption.

Main Methods:

Four healthy subjects received multiple oral doses of penicillamine under fasting conditions.
Two subjects received an additional dose post-meal.
Plasma levels were analyzed to determine kinetic parameters.

Main Results:

Fasting penicillamine administration resulted in a unique double-peak plasma concentration profile.

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Significant inter-subject variability was observed in pharmacokinetic parameters.

The half-life ranged from 1.66 to 3.15 hours, and plasma clearance from 530 to 2300 ml/min.

Postprandial dosing markedly reduced the extent of penicillamine absorption.

Conclusions:

Oral penicillamine exhibits complex absorption kinetics with potential for double peaks.
Food significantly impairs the oral bioavailability of penicillamine.
Individual pharmacokinetic variability necessitates careful dosing considerations.