Pharmacokinetics of chloroquine in Indian tribal and non-tribal healthy volunteers and patients with Plasmodium falciparum malaria

摘要

The pharmacokinetics of chloroquine was studied in Indian tribal and non-tribal healthy volunteers and patients infected with Plasmodium falciparum malaria, after a single dose of 600-mg chloroquine. Mean area under the curve (AUC), half-life (T-1/2) and peak concentration (C-max) in tribal P. falciparum patients were 18.79 +/- 5.82 mug h ml(-1), 115.94 +/- 57.71 h and 435 +/- 135.17 ng ml(-1) respectively, while in non-tribal P. falciparum patients they were 17.00 +/- 5.60 mug h ml(-1), 76.15 +/- 8.00 h and 454 +/- 193 ng ml(-1) respectively. Pharmacokinetic parameters did not appreciably differ between-tribal and non-tribal groups of subjects in healthy volunteers or in P. falciparum patients. However, the time to reach maximum concentration (T-max) was 8 h in tribal subjects and 4 h in non-tribal subjects. Mean ratio of AUC of chloroquine to desethylchloroquine in tribal P. falciparum patients was higher (4.26 +/- 1.34) than non-tribal subjects (3.41 +/- 0.66), suggesting reduced chloroquine metabolism in tribal subjects. However, the difference was statistically insignificant (t = 1.35, P < 0.5). Delayed T-max and impaired chloroquine metabolism may be associated with general health problems such as malnutrition, anaemia and parasitic infestations of the tribal population in India.