title: Plasma, erythrocyte and urine concentrations of chlorproguanil and two metabolites in man after different doses.
abstract: 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.
authors.affiliation: Liberian Institute for Biomedical Research, Charlesville, Margibi County.
authors.forename: E
authors.initials: E
authors.lastname: Petersen
authors.forename: H
authors.initials: H
authors.lastname: Flachs
authors.forename: B
authors.initials: B
authors.lastname: Høgh
authors.forename: A P
authors.initials: AP
authors.lastname: Hanson
authors.forename: A
authors.initials: A
authors.lastname: Björkman
authors.forename: E F
authors.initials: EF
authors.lastname: Hvidberg
mesh_terms: D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D002727:Proguanil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D014227:Triazines / Q000097:blood / Q000652:urine
chemical_list: D000962:Antimalarials; D014227:Triazines; C026009:cycloguanil; C007030:chlorproguanil; D002727:Proguanil