The erythromycin breath test for the prediction of drug clearance

The erythromycin breath test (EBT) is a putative probe of cytochrome P450 ( CYP) 3A4 activity in vivo. Therefore, the EBT might prove useful for the in dividualisation of doses of drugs that have a low therapeutic window (for e xample the immunosuppressants or cytotoxics) and are metabolised by CYP3A4. However, there is a lack of consensus as to how the EBT should be used to predict total body clearance (CL), and the results so far have been largely disappointing. We argue that the required assumption that individuals produce 5 mmol of CO 2/min per m(2) at rest is one of the problems with the existing EBT, as the literature suggests significant variability and possible gender difference s in this parameter. An examination of the EBT with a simple compartment mo del suggests that alternative parameters could be mon useful in the predict ion of CL. In particular, there is theoretical support for the use of the t ime-point at which breath radioactivity is maximal (t(max)) as a correlate for CL. This is in agreement with our recent study of the pharmacokinetics of erythromycin in patients with cancer.