EFFECTS OF FOOD ON THE PHARMACOKINETICS OF AMODIAQUINE IN HEALTHY VOLUNTEERS

Amodiaquine (AQ) is a 4-aminoquinoline derivative whichis intrinsically more active than the other 4-aminoquinoline, chloroquine, against Plasmodiumfalciparum parasites. The pharmacokinetic parameters ofamodiaquine and its active metabolite following theadministration of amodiaquine to healthy volunteers underfasted conditionS were compared with those when it wasco-administered with food.In an open, two-way crossover study, 16 healthyvolunteers fasted overnight and were randomized toreceive a single oral administration of 600 mg (3 tablets)of amodiaquine in the absence or presence of astandardized high-fat breakfast, administered 30 minbefore drug administration. Blood samples were collectedup to 192 h and amodiaquine and desethyl amodiaquinewere assayed by a validated HPLC method.Relative to the fasting state, the administration of a singledose of amodiaquine after a high-fat breakfast resulted indelayed median Tmax values (20 min for amodiaquine and3 h for desethylamodiaquine). The geometric mean ratios(GMR) of fed to fasting conditions indicated increasedCmax values for amodiaquine (GMR 1.40) (90% CI: 1.12-1.48) and desethylamodiaquine (GMR 1.48) (90% CI: 1.09-1.52) and increased AUC0-t values for amodiaquine (GMR1.62) (90% CI: 1.42-1.86) and for desethylamodiaquine(GMR 1.26) (90% CI: 1.12-1.36).Intake of AQ with a high fat meal resulted in a statisticallysignificant increase in blood levels of amodiaquine anddesethylamodiaquine which may affect its safety andtolerability. The findings of this study suggest thatamodiaquine should not be administered with a high-fatmeal