THE PHARMACOKINETICS OF 3 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 week s: once weekly 300 mg, twice weekly 200 mg and once daily 50 mg chloro quine, Plasma concentrations of chloroquine and metabolites were deter mined 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 f or the three regimens, ranging from 250-302 1 kg(-1), 374-479 h and 0. 44-0.58 1 h(-1) kg(-1) respectively. After the first week of all dosag e regimens, peak and trough concentrations of chloroquine were above 1 6 mu g l(-1), sufficiently suppressive for chloroquine-sensitive P. fa lciparum strains, These data suggest that once daily chloroquine could be combined with proguanil in a single tablet and should improve comp liance when given for malaria chemoprophylaxis.