TABLE 3.
Factors influencing ESC serum concentration (SC).
| References | CYP2C19 genotype | Dose | Sex | Age | Body weight | Smoking | Comedication |
| Bråten et al. (25) | X1 | – | |||||
| Jukić et al. (26) | X2 | ||||||
| Reis et al. (22) | X6 | – | X12 | – | – | –21 | |
| Reis et al. (21) | X7 | X9 | X13 | ||||
| Rudberg et al. (27) | X3 | ||||||
| Rudberg et al. (28) | X4 | ||||||
| Scherf-Clavel et al. (23) | X8 | X9 | –14 | X20 | |||
| Tsuchimine et al. (29) | X5 | X8 | X15 | –18 | |||
| Unterecker et al. (30) | –19 | ||||||
| Unterecker et al. (31) | –10 | –16 | |||||
| Waade et al. (32) | X | X11 | X17 | ||||
| Warrings et al. (24) | – |
X = correlation found; – = no correlation found; blank = not reported; bold = clinically relevant.
Genotype (if not specified other decrease/increase of ESC SC compared to CYP2C19*1/*1 group).
1Compared to baseline (no carriers of CYP2C19Null, CYP2C19*17, CYP2C:TG haplotypes): 1x/2x CYP2C:TG -16.7%/–24.8%; 1x/2x CYP2C19*17 –13.9%/–17.2%; 1x/2x CYP2C19Null (non–functioning alleles CYP2C19*2, *3 or *4) + 47%/ + 150%.
2CYP2C19*2/*2: + 230%; CYP2C19*2/*1: + 60%; CYP2C19*2/*17: + 40%; CYP2C19*1/*17: –10%; CYP1C19*17/*17: –20%.
3Non–dose–corrected SC: CYP2C19*2/*1: + 150%.
4Dose–adjusted SC: CYP2C19*17/*17: –42%; CYP2C19*1/*17: –13%; CYP2C19*17/def(*2 or *3 alleles): + 30%; CYP2C19*1/def: + 90%; CYP2C19def/def: + 470%.
5Significant difference among genotype groups in the dose–corrected steady–state SC.
Dose
6Dose–concentration linearity.
7Lower C/D ratios with increasing doses.
8ESC SC significantly increased with dose.
Sex
9Higher ESC SC in women vs men.
10No significant difference between males and females in the mean dose–corrected ESC SC.
11 + 80% higher C/D ratio in women vs men.
Age
12Higher age correlated with > ESC dose–normalized SC.
13 + 91% increase of ESC SC in subjects > 65y compared to subjects < 65 years at 10 mg/d.
14Linear regression analysis showed no influence of age (P = 0.301).
15Analysis of covariance: CYP2C19 genotypes and age were correlated with the steady–state ESC SC.
16No significant difference between patients < 60 years and patients > 60 years regarding the mean dose–corrected ESC SC.
17+40% higher mean C/D ratio in patients > 65 years, than in patients < 40 years (not significant in CYP2C19 PM, significant in other subgroups of CYP2C19 phenotype).
Body weight
18Analysis of covariance showed that CYP2C19 genotypes and body weight were not correlated with steady–state ESC SC.
19Referring to dose–corrected SC.
Smoking
20–24% lower ESC SC in smokers compared to non-smokers.
Comedication
21Concomitant medication did not interact with ESC. Women taking oral contraceptives had < metabolic ratio compared to women of the same age.