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

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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.

Original languageEnglish
JournalAmerican Journal of Tropical Medicine and Hygiene
Issue number3
Pages (from-to)199-205
Number of pages7
Publication statusPublished - Jun 1991

    Research areas

  • Adult, Aged, Antimalarials/blood, Chromatography, High Pressure Liquid, Erythrocytes/chemistry, Female, Humans, Male, Middle Aged, Proguanil/administration & dosage, Triazines/blood

ID: 203011961