In-vivo indices of enzyme activity: the effect of renal impairment on the assessment of CYP2D6 activity

Urinary drug:metabolite ratios and urinary recoveries of metabolites, have been used to assess specific enzyme activity non-invasively in vivo. These indices are potentially confounded by the effect of renal function. A recen t study of the effects of renal impairment has found discrepancies between different indices used to mark CYP2D6 activity based on sparteine and dextr omethorphan urinary recoveries. We have re-examined these experimental data from a theoretical viewpoint. The results suggest that the dependence of f ractional urinary recovery of metabolites on renal function varies with the importance of different elimination routes. Therefore, no consistent behav iour of this index is expected when markers with different pharmacokinetics are used. However, when collecting the urine until full recovery of drug a nd metabolite, drug:metabolite ratios show the same degree of dependence on renal function regardless of the marker. The application of the analysis t o the experimental data indicates that CYP2D6 activity is compromised in pa rallel with deterioration of renal function. Pharmacogenetics 9:277-286 (C) 1999 Lippincott Williams & Wilkins.