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1. Plasma and whole blood concentrations of proguanil and its two major metabolites cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) were measured by a sensitive h.p.l.c. technique in nine healthy adult male volunteers after a single oral dose of proguanil 200 mg. 2. Proguanil was absorbed with a median time to peak plasma concentration of 3 h (range 2-4 h). 3. Peak plasma concentrations of proguanil ranged between 150 and 220 (median 170) ng ml-1 compared with 12 to 69 (median 41) ng ml-1 for the active antimalarial metabolite CG, and 3 to 16 (median 11) ng ml-1 for CPB. Peak (mean +/- s.d.) plasma CG concentrations occurred 5.3 +/- 0.9 h and peak CPB concentrations occurred 6.3 +/- 1.4 h after oral administration of proguanil. 4. Whole blood concentrations of proguanil were approximately five times higher, and whole blood CPB concentrations were four times higher than corresponding plasma values, whereas plasma and whole blood concentrations of CG were similar. 5. A triexponential function was fitted to these data; mean (+/- s.d.) values for the AUC were 3046 +/- 313 ng ml-1 h for proguanil, 679 +/- 372 ng ml-1 h for CG and 257 +/- 155 ng ml-1 h for CPB. 6. Plasma and whole blood concentrations of proguanil and its metabolites declined in parallel with terminal elimination half-lives estimated as 16.1 +/- 2.9 h and 15.7 +/- 2.4 h, respectively. Mean residence times in plasma and whole blood were estimated as 21.2 +/- 4.9 and 19.3 +/- 2.4 h.

Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng.ml-1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng.h.ml-1.kg-1, respectively. Corresponding whole blood AUC values were 361 and 396 ng.h.ml-1.kg-1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng.ml-1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml-1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies.(ABSTRACT TRUNCATED AT 250 WORDS)