Summary
Although the absorption of verapamil is almost complete after oral administration, its bioavailability is low due to extensive hepatic first-pass metabolism. Besides large interindividual differences in first-pass metabolism, pronounced day-to-day intraindividual variations in first-pass metabolism are observed, leading to erroneous results in relative bioavailability studies. Stable isotope techniques, which permit simultaneous administration of a solution and a tablet, can successfully be used to overcome these difficulties. The method has the advantage that two experiments can be carried out in a single test. Furthermore, the number of subjects required in bioavailability studies can be greatly reduced. Using this technique the bioavailability of verapamil tablets (Isoptin® 80) relative to a stable labelled solution of verapamil was found to be 108.1%, with a 95% confidence interval between 89.1 and 127.1%.
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Eichelbaum, M., Dengler, H.J., Somogyi, A. et al. Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination. Eur J Clin Pharmacol 19, 127–131 (1981). https://doi.org/10.1007/BF00568399
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DOI: https://doi.org/10.1007/BF00568399