The pharmacokinetics of three multiple dose regimens of chloroquine: implications for malaria chemoprophylaxis.

The pharmacokinetics of chloroquine were studied in healthy volunteers who received one of three different multiple-dose regimens for 3 weeks: once weekly 300 mg, twice weekly 200 mg and once daily 50 mg chloroquine. Plasma concentrations of chloroquine and metabolites were determined by h.p.l.c. with fluorescence detection. The concentration-time course was fitted to a multiple-dose pharmacokinetic model. Volume of distribution, elimination half-life and clearance were not different for the three regimens, ranging from 250-302 l kg-1, 374-479 h and 0.44-0.58 l h-1 kg-1 respectively. After the first week of all dosage regimens, peak and trough concentrations of chloroquine were above 16 micrograms l-1, sufficiently suppressive for chloroquine-sensitive P. falciparum strains. These data suggest that once daily chloroquine could be combined with proguanil in a single tablet and should improve compliance when given for malaria chemoprophylaxis.