Human pharmacokinetics of proguanil and its metabolites
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Human pharmacokinetics of proguanil and its metabolites. / Bygbjerg, Ib Christian; Ravn, P; Rønn, A; Flachs, H; Hvidberg, E F.
In: Tropical Medicine and Parasitology, Vol. 38, No. 2, 01.06.1987, p. 77-80.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Human pharmacokinetics of proguanil and its metabolites
AU - Bygbjerg, Ib Christian
AU - Ravn, P
AU - Rønn, A
AU - Flachs, H
AU - Hvidberg, E F
PY - 1987/6/1
Y1 - 1987/6/1
N2 - The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds in plasma extracts as separate peaks. In four subjects peak plasma concentrations of proguanil (500 to 600 nmol/l) were reached after two to three hours, while cycloguanil and p-chlorophenylbiguanide showed a plateau after three and six hours, respectively. In the fifth subject peak concentrations of proguanil and cycloguanil appeared after seven hours. Trough concentrations (pre-dose in the morning) of proguanil and cycloguanil were about 200 and 100 nmol/l, respectively. Mean half-life of proguanil was estimated to approximately 20 h. The active metabolite cycloguanil constituted 30% of the total plasma drug concentration. The concentration of proguanil was higher in erythrocytes than in plasma, while that of cycloguanil was lower. Relevant clinical studies correlating plasma concentrations to the suppressive activity against malaria will be possible to perform based on the applied method and presented kinetic data.
AB - The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compounds in plasma extracts as separate peaks. In four subjects peak plasma concentrations of proguanil (500 to 600 nmol/l) were reached after two to three hours, while cycloguanil and p-chlorophenylbiguanide showed a plateau after three and six hours, respectively. In the fifth subject peak concentrations of proguanil and cycloguanil appeared after seven hours. Trough concentrations (pre-dose in the morning) of proguanil and cycloguanil were about 200 and 100 nmol/l, respectively. Mean half-life of proguanil was estimated to approximately 20 h. The active metabolite cycloguanil constituted 30% of the total plasma drug concentration. The concentration of proguanil was higher in erythrocytes than in plasma, while that of cycloguanil was lower. Relevant clinical studies correlating plasma concentrations to the suppressive activity against malaria will be possible to perform based on the applied method and presented kinetic data.
KW - Adult
KW - Biguanides
KW - Chemical Phenomena
KW - Chemistry
KW - Chromatography, High Pressure Liquid
KW - Erythrocytes
KW - Female
KW - Half-Life
KW - Humans
KW - Kinetics
KW - Male
KW - Proguanil
KW - Triazines
M3 - Journal article
C2 - 3629140
VL - 38
SP - 77
EP - 80
JO - Tropical Medicine and Parasitology
JF - Tropical Medicine and Parasitology
SN - 0177-2392
IS - 2
ER -
ID: 33891665