Plasma, erythrocyte and urine concentrations of chlorproguanil and two metabolites in man after different doses.

Failures in the prophylactic effect of the antimalarial biguanide chlorproguanil (Lapudrine) may be caused by insufficient levels of its active metabolite chlorcycloguanil. Concentrations of chlorproguanil, chlorcycloguanil and a second metabolite, dichlorophenylbiguanide, in plasma, erythrocytes and urine, were followed in 13 volunteers, using a HPLC assay. In an initial study the basic kinetics were investigated after an oral dose of 2 mg kg-1. In the main study, the concentration-time curves were followed for 1 week after an oral dose of 20 or 80 mg chlorproguanil, respectively, after either a single dose or one weekly dose for 5 weeks. Higher concentrations of all three compounds were found in erythrocytes than in plasma. The active substance, chlorcycloguanil, was below the probably effective concentration in erythrocytes 24 h after 20 mg chlorproguanil and 72 h after 80 mg. The urinary recovery was about 45% of the dose and t1/2 31-44 h, both higher than previously reported. The apparent clearance was 0.52-0.82 l h-1 kg-1, which is lower than previously found. It is suggested that improved dose regimens, e.g. a higher dose given once a week, should be clinically tested on basis of these kinetic results.