Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.
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.
Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
J
J
Nagy
H G
HG
Schipper
R P
RP
Koopmans
J J
JJ
Butter
C J
CJ
Van Boxtel
P A
PA
Kager
D000328:Adult; D015766:Albendazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001628:Beverages; D001682:Biological Availability; D002927:Cimetidine / Q000008:administration & dosage*; D002957:Citrus; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male
D000871:Anthelmintics; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D015766:Albendazole