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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CYP2D6 is primarily responsible for the metabolism of clomiphene.

Clomiphene is a first line treatment for anovulation, a common cause of infertility. Response to clomiphene is variable and unpredictable. Tamoxifen is structurally related to clomiphene, and also shows considerable variation in response. CYP2D6 and CYP3A4 are major contributors to the metabolism of tamoxifen. The aim of the present work was to define the role […]

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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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