Abstract

The effect of chloroquine on the pharmacokinetics of chlorpropamide was investigated in human volunteers. The study was carried out by administering chlorpropamide alone on healthy volunteers, and then chlorpropamide was co-administered with chloroquine. High performance liquid chromatography (HPLC) was used for the analysis of the plasma levels of chlorpropamide. The solvent used was acetonitrile/water (6:4) at pH 6.7. Ultrasphere ODS column, 4.6 × 25 cm, USA was used. The result from the chlorpropamide plasma level analysis shows that the absorption half-life (t_1/2a) and the time to maximum peak concentration (t_max) increased by 10% (P < 0.04) and 20% (P < 0.01), respectively. The absorption rate constant (K_a) and the maximum concentration (C_max) decreased by 30 and 16% (P < 0.02), respectively. The area under the curve (AUC_0-168) decreased significantly by 50% (P < 0.03). The plasma clearance of chlorpropamide increased significantly by 86% (P < 0.01).The volume of distribution (V_d) and the elimination half life(t_1/2el) decreased by 10%(p<0.03) and 47% (P < 0.01), respectively, while the elimination constant (k_el) increased by 100% (P < 0.02). Co-administration of chlorpropamide with chloroquine significantly (P < 0.05) impaired the absorption and elimination of chlorpropamide.

Key words: Pharmacokinetics, chlorpropamide, chloroquine, high performance liquid chromatography, half-life, absorption rate constant, elimination constant.