The pharmacokinetics of proguanil in human subjects following a single oral dose.

The pharmacokinetics of orally administered 200-mg dose of proguanil in volunteers, one African and one Caucasian, is described. The drug was rapidly absorbed reaching a peak concentration in the blood within 3 h, and declining slowly thereafter to give a terminal phase elimination half life of 11.20 +/- 4.10 h and a systemic clearance of 1.270 +/- 0.020 l/h/kg. The small apparent volume of distribution shows that the drug is confined mainly to the blood and is not extensively bound to tissues; it undergoes cyclic oxidation in the liver to cycloguanil--the active metabolite responsible for antimalarial activity. Cycloguanil was detected in the plasma 3 h after proguanil ingestion and reached peak concentration between 5 h and 6 h. Excretion of proguanil was rapid, 60% of the single dose passing through the renal system within 24 h.