Aims: Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ-SO) and sulphone (TCBZ-SO2) metabolites was investigated.
Methods: Two single doses (10 mg kg(-1)) of TCBZ were administered to 20 patients with fascioliasis. Ten patients were first given the drug after a high energy breakfast and then, 48 h later, after an overnight fast. The other 10 patients first received the drug in fasting state and then, 48 h later, after breakfast. A low energy breakfast was served 2 h after drug administration for fasting state.
Results: Compared with the fasting state, an increased AUC and Cmax after food intake (significant, P < 0.0001) was shown from the values of TCBZ, TCBZ-SO and TCBZ-SO2. The mean AUC for TCBZ (fasting: 1.55, fed: 5.72 micromol l(-1) h), TCBZ-SO (fasting: 177, fed: 386 micromol l(-1) h) and TCBZ-SO2 (fasting: 13.9, fed: 30.5 micromol l(-1) h) indicated a large availability increase with food and the strong systemic predominance of the active sulphoxide metabolite over the unchanged drug. (All patients were cured at the end of the trial except one who required a second course of two postprandial doses of triclabendazole (10 mg kg(-1) each). Tolerability to the treatment among the patients was good.
Conclusions: The administration of triclabendazole with food is recommended for improved systemic availability in patients with fascioliasis or paragonimiasis.
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| http://dx.doi.org/10.1046/j.1365-2125.1998.00725.x | DOI Listing |
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