Hepatic drug metabolism by CYP2D6 in critically ill adults with AKI: effect of phenotype and AKI severity

Introduction Hepatic drug metabolism by cytochrome P450 type 3A (CYP3A) is impaired in patients with acute kidney injury (AKI) [1]. The mechanisms underlying this are unclear. CYP2D6 is another clinically important hepatic CYP subtype, responsible for approximately 25% drug metabolism. Common phenotypic variation exists, the clinical relevance of which has not been previously demonstrated in the critically ill. Tramadol is a drug probe principally of CYP2D6 metabolism. M1 is formed by CYP2D6, and M2 by CYP3A4. In a pilot study, we showed that single time point determination of tramadol concentration 4 hours after IV tramadol bolus accurately predicts integral tramadol exposure and hence tramadol metabolism in critically ill adults [2]. Objectives We aimed to investigate if an association exists between CYP2D6 drug metabolism and AKI in critically ill adults. We also investigated the importance of genetically predicted CYP2D6 phenotype (poor, intermediate and extensive metabolisers) for drug metabolism in critically ill adults.