Effect of dose increase or cimetidine co-administration on albendazole bioavailability

The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to i mprove bioavailability. To analyze the assumed dose-dependent bioavailabili ty of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male volu nteers in a randomized cross-over study. To assess the effect of cimetidine (10 mg/kg twice daily), the drug was given with albendazole (20 mg/kg). A dose-dependent bioavailability was not observed. This was due to inter-indi vidual variability of the maximal concentration (C-max 38%-72%) of albendaz ole sulphoxide (ABZSX), the active metabolite of albendazole. C-max was 0.2 1 +/- 0.14 mg/L after 5 mg/kg and 0.39 +/- 0.19 mg/L after 30 mg/kg albenda zole (P = 0.217). Cimetidine tended to decrease C-max by 52% (P = 0.109) an d significantly inhibited ABZSX breakdown as indicated by the prolongation of ABZSX elimination half-life from 7.4 +/- 3.3 hr to 19.0 +/- 11.7 hr (P = 0.028). Remarkably, the inter-individual variability of C-max was signific antly lower during cimetidine co-administration: 14% versus 72%.