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European Journal of Clinical Pharmacology

, Volume 19, Issue 2, pp 127–131 | Cite as

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
  • M. Eichelbaum
  • H. J. Dengler
  • A Somogyi
  • G. E. von Unruh
Originals

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%.

Key words

verapamil tablets relative bioavailability intraindividual changes first-pass metabolism stable isotope technique 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • M. Eichelbaum
    • 1
  • H. J. Dengler
    • 1
  • A Somogyi
    • 1
  • G. E. von Unruh
    • 1
  1. 1.Department of MedicineUniversity of BonnBonn-VenusbergGermany

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