Cimetidine Albendazole

Nagy J, Schipper HG, Koopmans RP, Butter JJ, Van Boxtel CJ, Kager PA. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 2002 66(3) 260-263. 

Benzimidazoles (mebendazole or albendazole) have been the most used treatment, but a combination of albendazole plus praziquantel may be more effective than a benzimidazole on its own (Mohamed et at., 1998 Ayles et a/., 2002 El-On, 2003). As cimetidine increases benzimidazole serum concentrations it may enhance their activity (Bekhti and Pirotte, 1987 Wen et ai, 1994). Whilst for some patients chemotherapy is the sole treatment, even where there will be surgical intervention, treatment with benzimidazoles is recommended before surgery (Keshmiri et ai, 2001). A range of doses have been used for treatments of patients but 12-15 mg/kg/day over weeks or months may be best, although an emulsion... 

The poor intestinal absorption of albendazole, which may be enhanced by a fatty meal, contributes to difficulties in predicting its therapeutic response in echinococcosis. The effect of cimetidine co-administration on the systemic availability of albendazole has been studied in six healthy men (42). After an overnight fast, a single oral dose of albendazole (10 mg/kg) was administered on an empty stomach with water, a fatty meal, grapefruit juice, or grapefruit juice plus cimetidine. The systemic availability of albendazole was reduced by cimetidine. There were no adverse events. These results are consistent with presystemic metabolism of albendazole by CYP3A4. 

It is suggested that the interaction is caused by the enzyme inhibitory ae-tions of cimetidine, which result in a reduetion in the metabolism of albendazole and mebendazole. Cimetidine may also reduee albendazole absorption and minimise inter-patient variability by redueing gastrie aeid-ity, but the reduction in absorption appears to be outweighed by the enzyme-inhibitory effects. 

Wen H, Zhang HW, Muhmut M, Zou PF, New RRC, Qaig PS. Initial observaticn on albendazole in combination with cimetidine for the treatment of human c tic echinococcosis. Atm... 

A study in 6 healthy subjects given albendazole 20 mg/kg and cimetidine 10 mg/kg twice daily found that cimetidine significantly inhibited the metabolism of albendazole sulfoxide as indicated by an increase in its elimination half-life from 7.4 to 19 hours. Cimetidine also reduced inter-... 

Grapefruit juice increased albendazole sulfoxide levels by about threefold and shortened its half-life by 46%. When albendazole was given with grapefruit juice and cimetidine the peak plasma level was reduced from 760 to 410 micrograms/L. However, the level achieved with cimetidine and grapefruit juice was still greater than that achieved when albendazole was given with water. 

Adebayo GI, Mabadeje AFB. Theophylline disposition — effects of cimetidine, mebendazole and albendazole. Aliment Pharmacol Ther 9ZZ) 2, 341-6,... 

---