Effects of Food on the Pharmacokinetics of Amodiaquine in Healthy Volunteers

Amodiaquine (AQ) is a 4-aminoquinoline derivative which is intrinsically more active than the other 4- aminoquinoline, chloroquine, against Plasmodium falciparum parasites. The pharmacokinetic parameters of amodiaquine and its active metabolite following the administration of amodiaquine to healthy volunteers under fasted conditionS were compared with those when it was co-administered with food.

In an open, two-way crossover study, 16 healthy volunteers fasted overnight and were randomized to receive a single oral administration of 600 mg (3 tablets) of amodiaquine in the absence or presence of a standardized high-fat breakfast, administered 30 min before drug administration. Blood samples were collected up to 192 h and amodiaquine and desethyl amodiaquine were assayed by a validated HPLC method.

Relative to the fasting state, the administration of a single dose of amodiaquine after a high-fat breakfast resulted in delayed median Tmax values (20 min for amodiaquine and 3 h for desethylamodiaquine). The geometric mean ratios (GMR) of fed to fasting conditions indicated increased Cmax 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 (GMR 1.62) (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 statistically significant increase in blood levels of amodiaquine and desethylamodiaquine which may affect its safety and tolerability. The findings of this study suggest that amodiaquine should not be administered with a high-fat meal.