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 improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male volunteers 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-individual variability of the maximal concentration (Cmax 38%-72%) of albendazole sulphoxide (ABZSX), the active metabolite of albendazole. Cmax was 0.21+/-0.14 mg/L after 5 mg/kg and 0.39+/-0.19 mg/L after 30 mg/kg albendazole (P = 0.217). Cimetidine tended to decrease Cmax by 52% (P = 0.109) and 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 Cmax was significantly lower during cimetidine co-administration: 14% versus 72%.
Schipper
H G
HG
Department of Internal Medicine, Tropical Medicine and AIDS, Academic Medical Center, The Netherlands. h.g.schipper@amc.uva.nl
Koopmans
R P
RP
Nagy
J
J
Butter
J J
JJ
Kager
P A
PA
Van Boxtel
C J
CJ
D000284:Administration, Oral; D000328:Adult; D015766:Albendazole / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000871:Anthelmintics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002927:Cimetidine / Q000008:administration & dosage* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004443:Echinococcosis / Q000188:drug therapy; D006801:Humans; D008297:Male; D012016:Reference Values
D000871:Anthelmintics; D002927:Cimetidine; D015766:Albendazole