Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.

Abstract

Abstract. 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 (C max ) 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 ‫ס‬ 0.031). When grapefruit juice was combined with cimetidine, C max was significantly lower than with grapefruit juice alone (0.41 ± 0.29 mg/l and 0.76 ± 0.37 mg/l, respectively; P ‫ס‬ 0.022). The area under the concentration-time curve from 0 to infinity (AUC 0-⍀ ) 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 ‫ס‬ 1.000). Grapefruit juice shortened T 1/2 by 46% (P ‫ס‬ 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.

Death Related to Albendazole-Induced Pancytopenia: Case Report and Review

“…Modifications in bioavailability have been observed with the co-ingestion with a fatty meal, which more than triples the peak concentration (Cmax) of albendazole sulfoxide, as does grapefruit ingestion. 11,15 While there are no published studies of albendazole pharmacokinetics specifically in individuals with cirrhosis, observations in individuals with extrahepatic obstruction have shown a doubling in the Cmax and an increased half-life (T 1/2 ). 16 Studies in healthy volunteers also demonstrate albendazole-induced hepatic oxidizing enzymatic induction with a reduced T 1/2 and area under the curve in multi-dosing studies.…”

“…10 Albendazole undergoes virtually 100% first-pass metabolism in the liver, and is rapidly converted to albendazole sulfoxide by both the microsomal flavin mono-oxidase and P450 CYP3A enzymes. 11 It then undergoes partial further metabolism to albendazole sulfone via a separate P450-dependent enzyme CYP2C. 12,13 Pharmacokinetic studies have demonstrated significant intra-individual and inter-individual variation in peak dose (Cmax) following albendazole ingestion among healthy volunteers.…”

Improvement of Albendazole Dissolution by Preparing Microparticles Using Spray-Drying Technique

“…Moreover, increased systemic bioavailability of albendazole was reported when the drug co-administered with a fatty meal [11], fruit juice [12], cosolvent [13], or with surfactants [14].…”

Relative Bioavailability of Three Newly Developed Albendazole Formulations: a Randomized Crossover Study with Healthy Volunteers

“…To inhibit CYP3A4 isozyme-related ABZSX degradation, albendazole was coadministered with cimetidine. However, this caused a 52% decrease in ABZSX C max values (probably due to inhibition of gastric acid secretion) (15,17), suggesting that absorption is pH dependent. When coadministered with grapefruit juice, the ABZSX C max was enhanced 3.2-fold, probably due to inhibition of the intraluminal degradation of albendazole by CYP3A4 enzymes (15).…”

“…When combined with a fatty meal, administration of albendazole sulfoxide (ABZSX) increased the maximum concentration of drug in serum (C max ) 4.5-to 9-fold (1,7,12,15). To inhibit CYP3A4 isozyme-related ABZSX degradation, albendazole was coadministered with cimetidine.…”