Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination. Studies of the relative bioavailability of verapamil tablets

Eur J Clin Pharmacol. 1981 Jan;19(2):127-31. doi: 10.1007/BF00568399.

Abstract

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%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability*
  • Deuterium
  • Female
  • Humans
  • Kinetics
  • Male
  • Tablets
  • Verapamil / metabolism*

Substances

  • Tablets
  • Deuterium
  • Verapamil