Probleme der Bestimmung der Bioverfügbarkeit und Bioäquivalenz von Arzneistoffen

Summary

Problems in the estimation of bioavailability and bioequivalence of drugs

In order to get an optimum therapeutic effect, drugs must be released from drug formulations with an optimum releaserate and to the maximum extent possible. Drug products of different companies, which contain the same amount of the same drug, must have comparable bioavailabilities; they should be bioequivalent. The following two problems are given special attention:

• 1) In which cases is an estimation of bioavailability and bioequivalence especially important?

• 2) Which methods are available for the estimation of bioavailability?

Bioavailability studies must be required for drug products if the active ingredient has not yet been introduced into the market. The importance of bioavailability or bioequivalence problems for products with well known drug substances depends on pharmacological, pharmacokinetic and physical properties of the drug as well as on pharmaceutical technological formulation factors. Bioavailability and bioequivalence problems occur especially with solid drug formulations with poorly soluble drugs, i. e. tablets or capsules. Most important for estimation of biopharmaceutical parameters are in vivo methods in human subjects. Much discussion has arisen during recent years on the question, how far dissolution behaviour as an in vitro test can be used for an index of bioavailability or bioequivalence. We have to differentiate here between in vitro methods which correlate well with in vivo experiments and those that do not. If a discrepancy exists between in vivo and in vitro bioavailability results then the in vivo results take precedence.