title: Traveller's diarrhoea; a controlled study of its effect on chloroquine and proguanil absorption.
abstract: The potential for traveller's diarrhoea to impair proguanil and chloroquine absorption and cause chemoprophylaxis failure was investigated in a study involving recently returned travellers who were either asymptomatic or presented with diarrhoea. A routine dose of chemoprophylaxis was administered to 12 travellers with diarrhoea and 12 asymptomatic subjects. The subjects undertook a lactulose-mannitol intestinal permeability test and were bled hourly after prophylaxis ingestion. Plasma analysis of chloroquine and proguanil from serial samples revealed a significantly lower proguanil Cmax (146 ng/mL vs. 196 ng/mL, P = 0.05), and longer tmax (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) but the difference did not quite reach levels of significance. Chloroquine kinetics were similar in both groups. The diarrhoea cohort had a three-fold higher lactulose absorption, influencing the mean lactulose mannitol: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.
authors.affiliation: Travel Clinic, Hospital for Tropical Diseases, London, UK.
authors.forename: R H
authors.initials: RH
authors.lastname: Behrens
authors.forename: R B
authors.initials: RB
authors.lastname: Taylor
authors.forename: A S
authors.initials: AS
authors.lastname: Low
authors.forename: B
authors.initials: B
authors.lastname: Warburton
authors.forename: D
authors.initials: D
authors.lastname: Pryce
mesh_terms: D000328:Adult; D002738:Chloroquine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003967:Diarrhea / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D002727:Proguanil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014195:Travel
chemical_list: D002738:Chloroquine; D002727:Proguanil