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Validation of the hepatic blood flow rate model for verapamil first-pass metabolism

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Summary

The bioavailability of a new retard tablet formulation of verapamil was investigated in a randomized cross-over bioequivalence study on 12 healthy subjects. The drug was given in the form of a single 240-mg oral dose of a new retard tablet formulation, or as a standard retard tablet at the same dose to all subjects, followed by a single intravenous (i.v.) dose of 5 mg to 8 of the 12 subjects. Plasma verapamil concentrations were determined by a high performance liquid chromatography (HPLC) method. The bioavailability of the new peroral retard formulation was (20.00±4.30)% and was in reasonable agreement with that determined for the already registered verapamil retard formulation, i.e. (19.46±4.02)%, thereby indicating bioequivalence. For the prediction of systemic availability and estimation of the first-pass metabolism, only based on the data for peroral plasma levels, a hepatic blood flow rate limited model was used. In our experience, this model has been found to be extremely useful in providing reasonable estimates of verapamil first-pass effect.

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  1. Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Novi Sad, Republic of Serbia

    Jovan Popović

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  1. Jovan Popović
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Popović, J. Validation of the hepatic blood flow rate model for verapamil first-pass metabolism. Eur. J. Drug Metabol. Pharmacokinet. 32, 13–19 (2007). https://doi.org/10.1007/BF03190985

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  • DOI: https://doi.org/10.1007/BF03190985

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