Co-administration of thiabendazole or artemisinin with CYP1A2 substrates could result in clinically significant effects. Our results highlight the validity of in vitro data in predicting in vivo CYP inhibition. The formation of paraxanthine seems to be a better indicator of in vivo CYP1A2 activity than caffeine levels.
The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (Dawaquin) and a plain formulation (Shellyquine) 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 (Cpmax ng/mL). The AUC and Cpmax for Shellyquine were 4396.3 +/- 833 ng mL(-1) h and 162 +/- 14 ng/mL, respectively. The AUC and Cpmax 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 Cpmax 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.
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