Abundance of Hepatic Transporters in Caucasians: A Meta-analysis

The aim of this study was to derive quantitative abundance values for key hepatic transporters suitable for in vitro-in vivo extrapolation (IVIVE) within a physiologically-based pharmacokinetic modeling framework. A meta-analysis was performed whereby abundance measurements, sample preparation method and donor demography were collated from literature. In order to define values for a healthy Caucasian population, […]

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Are There Differences in the Catalytic Activity per Unit Enzyme of Recombinantly Expressed and Human Liver Microsomal Cytochrome P4502C9? A Systematic Investigation into Inter-system Extrapolation Factors

The ‘relative activity factor’ (RAF) compares the activity per unit of microsomal protein in recombinantly expressed cytochrome P450 enzymes (rhCYP) and human liver without separating the potential sources of variation (i.e. abundance of enzyme per mg of protein or variation of activity per unit enzyme). The dimensionless ‘inter-system extrapolation factor’ (ISEF) dissects differences in activity […]

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Assessment of In Vivo CYP2D6 Activity: Differential Sensitivity of Commonly Used Probes to Urine pH

Drug/metabolite ratios (MRs) are used as in vivo markers of enzyme activity. The ratios are potentially confounded by the renal clearance of the drug (urine-based MRs) or metabolite (plasma-based MRs). The authors have investigated the relative sensitivity of urinary MR of 3 in vivo probe substrates of CYP2D6 debrisoquine (DB), dextromethorphan (DM), and metoprolol (MP) […]

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