Comparative Bioavailability of Oral Sugar-Coated and Plain Formulation of Chloroquine Phosphate Marketed in Tanzania

Abstract

The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (Dawaquin^R) and a plain formulation (Shellyquine^R) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL⁻¹ h) and the peak blood chloroquine concentration (Cp_max ng/mL). The AUC and Cp_max for Shellyquine were 4396.3 ± 833 ng mL⁻¹ h and 162 ± 14 ng/mL, respectively. The AUC and Cp_max for Dawaquin were 2060 ± 339 ng mL⁻¹ h and 56.6 ± 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cp_max for Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.