Plasma, erythrocyte and urine concentrations of chlorproguanil and two metabolites in man after different doses
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Plasma, erythrocyte and urine concentrations of chlorproguanil and two metabolites in man after different doses. / Petersen, E; Flachs, H; Høgh, B; Hanson, A P; Björkman, A; Hvidberg, E F.
In: American Journal of Tropical Medicine and Hygiene, Vol. 94, No. 3, 06.1991, p. 199-205.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma, erythrocyte and urine concentrations of chlorproguanil and two metabolites in man after different doses
AU - Petersen, E
AU - Flachs, H
AU - Høgh, B
AU - Hanson, A P
AU - Björkman, A
AU - Hvidberg, E F
PY - 1991/6
Y1 - 1991/6
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Antimalarials/blood
KW - Chromatography, High Pressure Liquid
KW - Erythrocytes/chemistry
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Proguanil/administration & dosage
KW - Triazines/blood
M3 - Journal article
C2 - 2051526
VL - 94
SP - 199
EP - 205
JO - Journal. National Malaria Society
JF - Journal. National Malaria Society
SN - 0002-9637
IS - 3
ER -
ID: 203011961