TRAVELERS DIARRHEA - A CONTROLLED-STUDY OF ITS EFFECT ON CHLOROQUINE AND PROGUANIL ABSORPTION

The potential for traveller's diarrhoea to impair proguanil and chloro quine absorption and cause chemoprophylaxis failure was investigated i n a study involving recently returned travellers who were either asymp tomatic or presented with diarrhoea. A routine dose of chemoprophylaxi s was administered to 12 travellers with diarrhoea and 12 asymptomatic subjects. The subjects undertook a lactulose-mannitol intestinal perm eability test and were bled hourly after prophylaxis ingestion. Plasma analysis of chloroquine and proguanil from serial samples revealed a significantly lower proguanil C-max (146 ng/mL vs. 196 ng/mL, P=0.05), and longer t(max) (3.1 h vs. 2.6 h, P=0.05) in the diarrhoea cohorts. The absorption coefficient was lower for proguanil (0.57 vs. 0.76) bu t the difference did not quite reach levels of significance. Chloroqui ne kinetics were similar in both groups. The diarrhoea cohort had a th ree-fold higher lactulose absorption, influencing the mean lactulose m annitol:ratio, 0.114+/-0.17 compared to the control ratio of 0.02+/-0. 01 (P=0.04). Symptomatic subjects had impaired mucosal function which reduced the absorption of proguanil but not chloroquine, a phenomenon which may reduce prophylactic efficacy.