Pharmacokinetic evaluation of different generic triclabendazole formulations in heifers

Abstract

AIMS: To assess the comparative drug systemic exposure of a reference (RF) and four test (Test I, Test II, Test III and Test IV) formulations of triclabendazole (TCBZ) in heifers.

METHODS: Thirty Holstein heifers were randomly distributed into five groups (n=6 per group). Animals in the RF group received the reference formulation (Fasinex), and those in the other groups received different commercially available TCBZ formulations (Test I, Test II, Test III and Test IV). All treatments were orally administered at 12 mg/kg bodyweight. The concentrations of TCBZ metabolites in plasma between 0 and 168 hours after treatment were quantified by high-performance liquid chromatography (HPLC).

RESULTS: Triclabendazole sulphoxide (TCBZ.SO) and TCBZ-sulphone (TCBZ.SO₂) were the only analytes recovered in plasma. Only the Test I formulation did not differ from the RF for all pharmacokinetic parameters measured for either metabolite (p>0.8). The TCBZ.SO area under the concentration vs. time curve for Test II formulation (268.9 µg.h/mL) was lower, and for Test III (619.9 µg.h/mL) and Test IV (683.4 µg.h/mL) was higher, than the RF (418.1 µg.h/mL) (p<0.005).

CONCLUSION: Based on the currently available bioequivalence criteria, the only test formulation under evaluation that could be considered equivalent to the RF was the Test I formulation, which demonstrated an equivalent systemic exposure for the active TCBZ.SO metabolite. This comparison of TCBZ pioneer and test formulations in cattle raises awareness of the need for further quality control for drug approval in the veterinary pharmaceutical field in many regions of the world.

KEY WORDS:

• Flukicidal control
• triclabendazole
• generic formulations
• bioequivalence

Acknowledgements

The authors would like to acknowledge Dr. Gottfried Büscher, from Novartis Animal Health Inc., Basel, Switzerland, who kindly provided TCBZ and TCBZ.SO and TCBZ.SO₂ pure reference standards. This research was supported by a grant from the European Commission.