Steady-State Kinetics of Proguanil and Its Active Metabolite, Cycloguanil, in Man

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Abstract
The pharmacokinetics of proguanil and its active metabolite, cycloguanil, were determined at steady-state in 6 healthy male volunteers after daily administration of 2 Paludrine® tablets (200 mg proguanil hydrochloride). A maximum plasma proguanil concentration of 130.3 ± 16.0 ng/ml (mean ± SD) was reached at 3.8 ± 1.3 h while a maximum cycloguanil concentration of 52.0 ± 15.2 ng/ml was obtained at 5.3 ± 1.0 h after dosing. The elimination half-lives of proguanil and cycloguanil were 14.5 ± 3.0 h and 11.7 ± 3.1 h, respectively. The plasma clearance of proguanil was 1.43 ± 0.33 1/h/kg and the apparent volume of distribution was 30.7 ± 12.3 1/kg. Renal clearance of proguanil (0.33 ± 0.19 1/h/kg) was about 23% of the plasma clearance and 35.6 ± 9.6% of the oral dose was recovered as proguanil and cycloguanil.