THE PHARMACOKINETICS AND ACTIVATION OF PROGUANIL IN MAN - CONSEQUENCES OF VARIABILITY IN DRUG-METABOLISM

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. 1990 The British Pharmacological Society