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. 1990 Oct;30(4):593-8.
doi: 10.1111/j.1365-2125.1990.tb03818.x.

The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism

N A Helsby  1 , S A Ward, G Edwards, R E Howells, A M Breckenridge
Affiliations

The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism

N A Helsby et al. Br J Clin Pharmacol. 1990 Oct.

Abstract

1. Based on the ratio of drug to active metabolite excreted in urine approximately 3% of a healthy Caucasian population showed a reduced ability to convert proguanil to cycloguanil. 2. Pharmacokinetic analysis showed that this observation resulted from a reduced oral clearance of proguanil in these individuals (245, 534 and 552 ml min-1) compared with the rest of the population (858 +/- 482 ml min-1). 3. Peak plasma concentrations of active metabolite were significantly lower in these subjects (54.2, 26.8 and 51.7 ng ml-1) compared with the rest of the population (141 +/- 45.2 ng ml-1). 4. The observed variability may result from the polymorphic metabolism of proguanil in man.

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