Effect of grapefruit juice or cimetidine
coadministration on albendazole bioavailability.
Nagy J, Schipper HG, Koopmans RP, Butter JJ, Van Boxtel CJ, Kager PA.
Department of Internal Medicine, Academic Medical Center, Amsterdam, The
Netherlands.
The assumed metabolic breakdown of albendazole by mucosal CYP3A4 enzymes was
studied by coadministering albendazole (10 mg/kg) with grapefruit juice.
Concentrations of albendazole sulfoxide (ABZSX), the active metabolite of
albendazole, were compared with those after albendazole was administered with
water, a fatty meal, or grapefruit juice plus cimetidine (10 mg/kg). In
comparison to water, maximum ABZSX concentration (Cmax) was enhanced 6.5-fold by
a fatty meal (from 0.24 +/- 0.09 mg/l to 1.55 +/- 0.30 mg/l; mean +/- SD; P <
0.001) and 3.2-fold by grapefruit juice (from 0.24 +/- 0.09 mg/l to 0.76 +/-
0.37 mg/L; P = 0.031). When grapefruit juice was combined with cimetidine, Cmax
was significantly lower than with grapefruit juice alone (0.41 +/- 0.29 mg/l and
0.76 +/- 0.37 mg/l, respectively; P = 0.022). The area under the
concentration-time curve from 0 to infinity (AUC(0-omega)) followed a comparable
pattern. Half-life (T(1/2)) was 8.8 +/- 4.2 hr and 8.2 +/- 4.3 hr after
administration with water or a fatty meal (P = 1.000). Grapefruit juice
shortened T(1/2) by 46% (P = 0.026). We hypothesize that albendazole is
metabolized by CYP3A4 enzymes in the intestinal mucosa. This process can be
inhibited by grapefruit juice. Cimetidine decreased albendazole bioavailability.