COMPARISON OF THE DAPSONE RECOVERY RATIO AND THE ERYTHROMYCIN BREATH TEST AS IN-VIVO PROBES OF CYP3A ACTIVITY IN PATIENTS WITH RHEUMATOID-ARTHRITIS RECEIVING CYCLOSPORINE

Introduction: Cytochrome P4503A (CYP3A) is primarily responsible for t he metabolism of cyclosporine and that of many other drugs. Several su bstrates of CYP3A have been investigated for use as pharmacologic prob es to predict the CYP3A-metabolizing capacity of an individual and, th erefore, the disposition of other CYP3A substrate drugs. One such meas ure of CYP3A activity is the C-14 erythromycin breath test, which has been applied to the prediction of cyclosporine disposition. However, t he test has practical limitations. Because of this, the 0- to 8-hour u rinary dapsone recovery ratio has been studied as an alternative and m ore practical probe of CYP3A activity. Methods: The dapsone recovery r atio and the C-14 erythromycin breath test were correlated with cyclos porine concentrations in 16 patients with rheumatoid arthritis to dete rmine the usefulness of the dapsone recovery ratio as an alternative t o the C-14 erythromycin breath test The erythromycin breath test showe d a fourfold variation between subjects and correlated weakly with tro ugh cyclosporine concentrations (r = -0.50, p < 0.05), whereas the dap sone recovery ratio varied only approximately twofold between subjects and did not correlate with trough cyclosporine concentrations (r = 0. 02, p = 0.94). The correlation between the dapsone recovery ratio and the erythromycin breath test (r = 0.22, p = 0.41) was not significant. Conclusions: These data suggest that results obtained with one probe in vivo may not apply to another CYP3A substrate. The poor quantitativ e relationship between cyclosporine concentrations and the erythromyci n breath test limits its usefulness in the prediction of an individual 's cyclosporine dose requirement.