TABLE 7.

Genetic and environmental effects on the CYP3A probe drugs and biomarkers.

Biomarker	Midazolam (AUC)		1-OH-midazolam (AUC)		4ß-OH-cholesterol		6ß-OH-cortisol
Factors	r2* (p)	Coefficient	r2 (p)	Coefficient	r2 (p)	Coefficient	r2 (p)	Coefficient
All	0.29 (<0.001)		0.15 (0.03)		0.24 (<0.001)		0.10 (0.02)
Sex	0.03 (0.04)	74.51		11.79		−3.32		−9.28
Age		−0.60	0.05 (0.01)	−1.78		0.16		0.94
Lean body weight	0.08 (0.001)	−7.29		−1.74.		−0.20		−1.35
Smoking status		−21.79		1.46		3.28		−8.66
Oral contraceptives	0.05 (0.008)	−63.18	0.05 (0.02)	−31.33		−2.57		3.37
CYP3A4*22	0.08 (0.001)	169.57		−12.53		−8.21	0.05 (0.02)	−127.40
CYP3A5*3		32.33		29.27	0.04 (0.02)	−6.30		0.70

*The correlation is given for the model with all factors studied and below the partial correlation coefficients are given for significant factors only. For midazolam, coefficients indicate higher AUC in males, decrease with higher lean body weight, lower AUC with current use of contraceptives and higher AUC in carriers of CYP3A4*22. The r² indicates the fraction of the total variation explained by all variables or by the respective factors. For 4ß-OH-cholesterol, coefficients indicate decrease of AUC per CYP3A5*3 allele. 6ß-OH-cortisol: Coefficients indicate decrease per CYP3A4*22 allele. The sample included no homozygous, but 4 heterozygous carriers of the CYP3A4*22 allele (3.4%) and no homozygous, but 16 heterozygous carriers of the CYP3A5*1 allele (13.8%).