Effect of grapefruit juice on plasma chloroquine kinetics in mice.

1. It is known that grapefruit juice (GFJ) may interact with drugs concomitantly administered by inhibiting first-pass metabolism during the intestinal absorption phase. However, its interaction with chloroquine has not been studied previously. 2. Grapefruit juice (4 mL/kg) was given orally to mice 1 h prior to oral administration of chloroquine (100 mg/kg) and the concentration of the latter drug was measured fluorometrically in the plasma 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 18 and 24 h after its administration. 3. The mean (+/-SEM) of area under the curve values after administration of water +/- control) and GFJ were 5.34 +/- 0.38 and 7.01 +/- 0.66 mg.h/L, respectively. The corresponding mean C(max) values were 763.4 +/- 39.1 and 859.2 +/- 45.2 mg/L and the corresponding T(max) values (median) were 2.65 and 2.95 h. 4. The results suggest that GFJ coingestion increased the plasma concentration of chloroquine and altered some kinetic parameters of chloroquine. The clinical significance of this interaction in patients with malaria needs to be investigated.