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.
| Original language | English |
|---|---|
| Journal | American Journal of Tropical Medicine and Hygiene |
| Volume | 94 |
| Issue number | 3 |
| Pages (from-to) | 199-205 |
| Number of pages | 7 |
| ISSN | 0022-5304 |
| Publication status | Published - Jun 1991 |
Keywords
- Adult
- Aged
- Antimalarials/blood
- Chromatography, High Pressure Liquid
- Erythrocytes/chemistry
- Female
- Humans
- Male
- Middle Aged
- Proguanil/administration & dosage
- Triazines/blood