THE EFFECTS OF CHLOROQUINE, PARACETAMOL AND PROMETHAZINE ON THE PHARMACOKINETICS OF CHLORPROPAMIDE IN HUMAN VOLUNTEERS
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- NGN 3000
ABSTRACT
The effect of chloroquine, paracetamol and Promethazine on the pharmacokinetic profile of chlorpropamide was investigated in human subjects. The batches of chlorpropamide, chloroquine, paracetamol and Promethazine used were subjected to quality control studies using official methods. The drugs complied with the B.P (1993) requirements stated in their monographs. A high performance liquid chromatography (HPLC) method was developed for the analysis of plasma chlorpropamide concentration. Pharmacokinetic parameters of chlorpropamide were derived with Winnonlin standard noncompartment software programme. About 16%, 14% and 15% decrease in the mean maximum concentration (Cmax) of chlorpropamide was observed following oral administration of chlorpropamide with chloroquine, paracetamol and Promethazine respectively. About 44%, 11% and 30% decrease in the area under curve (AUC) of chlorpropamide was observed following concurrent administration of chlorpropamide with chloroquine, paracetamol and Promethazine respectively. The plasma clearance of chlorpropamide increased by 86% following chlorpropamide interaction with chloroquine. xii The absorption half-life (t½a) of chlorpropamide increased by 4%, 85% and 69% when concomitantly administered with chloroquine, paracetamol and Promethazine respectively. The elimination constant (Kel) of chlorpropamide was found to have increased by 100% and decreased by 31% following concomitant administration of chlorpropamide with chloroquine and paracetamol respectively. The elimination half-life (t½el) of chlorpropamide was found to have decreased by 47% and increased by 13% and 29% following concomitant administration to chlorpropamide with chloroquine, paracetamol and Promethazine respectively. The study implied impaired absorption and elimination of chlorpropamide by chloroquine, paracetamol and Promethazine.
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