A quantitative approach to hepatic clearance prediction of metabolism by aldehyde oxidase using custom pooled hepatocytes.

We describe the usability of human pooled hepatocytes for non-CYP metabolism evaluation and an in vivo–in vitro correlation analysis for aldehyde oxidase (AO) substrate compounds using pooled hepatocytes.By comparing intrinsic clearance values of 18 compounds primarily metabolized by AO, UDP-glucuronosyltransferase, carbonyl/aldo-keto reductase, flavin-containing monooxygenase, and monoamineoxidase in individual hepatocytes and pooled hepatocytes from the same individual donors, intrinsic clearance in the pooled hepatocytes was ±30% of the average clearance value in individuals for 15 of 18 compounds, suggesting that pooled hepatocytes maintained the average activity of the individual hepatocytes.Although the results of an in vivo–in vitro correlation analysis for AO substrate compounds showed a trend toward under-prediction, the underestimation ratios for all AO substrates were nevertheless comparable (7.2- to 14.9-fold), suggesting that hepatic clearance prediction for these compounds can be quantified ...