Estimated CYP2C19 enzyme abundance and variability in relation to genotypes
Based on in vitro formation rate of 4′-hydroxymephenytoin at a single concentration of S-mephenytoin (50 µM) in 123 HLMs. Five samples (two CYP2C19*1/*2 and three CYP2C19*2/*2) yielded values below quantitative level and were excluded from the 128 genotyped HLMs. The “null” refers to CYP2C19*2 or *4 allele.
| *17/*17 | *1/*17 | *1/*1 | *17/null | *1/nulla | null/null | |
|---|---|---|---|---|---|---|
| N | 4 | 38 | 51 | 9 | 18 | 3 |
| Mean activityb | 0.0450 | 0.0434 | 0.0249 | 0.0209 | 0.0102 | 0.0012 |
| S.D. | 0.0513 | 0.0655 | 0.0325 | 0.0158 | 0.0116 | 0.0007 |
| CV (%) | 114 | 151 | 131 | 75 | 116 | 55 |
| Mean baseline-corrected activityb | 0.0438 | 0.0422 | 0.0236 | 0.0197 | 0.0089 | 0 |
| Scaling factor | 1.85 | 1.79 | 1.00 | 0.83 | 0.38 | 0 |
| CYP2C19 abundance estimatec | 26 | 25 | 14d | 12 | 5.3 | 0 |
| CYP2C19 abundance CV estimate (%) | 117 | 155 | 138 | 80 | 130 | 0 |
↵a CYP2C19*1/*4 and CYP2C19*1/*2 were combined into one CYP2C19*1/null group, as both genotypes were predicted to be intermediate metabolizers (de Morais et al., 1994; Ferguson et al., 1998).
↵b Unit of activity is nmol 4′-hydroxymephenytoin/min per milligram microsomal protein.
↵c Unit of enzyme abundance is pmol/mg protein.
↵d SimCYP default value.