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The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism.
Author(s) -
Helsby NA,
Ward SA,
Edwards G,
Howells RE,
Breckenridge AM
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03818.x
Subject(s) - proguanil , pharmacokinetics , metabolite , urine , pharmacology , active metabolite , population , drug metabolism , drug , metabolism , chemistry , medicine , immunology , environmental health , chloroquine , malaria
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.