Absolute bioavailability studies in humans: the merits of accelerator mass spectrometry

Obtaining information on the metabolic fate of a drug in humans is a key requirement in drug development. Of the various metabolic (pharmacokinetic) parameters, such as AUC, half-life, C max and so on, absolute bioavailability is one PK parameter that is not routinely measured. Although some data on the bioavailability of new drugs has to be submitted as part of the drug approval process, pharmaceutical companies may not necessarily perform a full bioavailability study in humans in every case. There are, nevertheless, certain situations where ignoring the need for an absolute bioavailability study might be unwise. For example, an orally administered anti-infective that is poorly absorbed may have to be given at doses that have adverse effects on gut microflora, leading to diarrhoea with the accompanying side effects. More generally, bioavailability determined from animal models is not always predictive of that in humans, and unexpected low bioavailability in humans is perhaps not that uncommon. There are therefore good reasons to perform an absolute bioavailability study in humans, although for reasons of time and cost pharmaceutical companies are generally very reluctant to do so, unless absolutely necessary.