Table 2.

Metabolic ratios (MR) (mean ± SD [95% confidence intervals on differences^*]) following the administration of probe substrates alone or in combination

Enzyme	n	Metoprolol alone	Tolbutamide alone	3 drug	4 drug	5 drug	P value
CYP3A4	10	ND	ND	0.32 ± 0.15[week 3-4: -0.09, 0.23]	0.25 ± 0.16[week 4-5: -0.23, 0.10]	0.32 ± 0.13[week 3-5: -0.16, 0.17]	0.5
CYP2D6 EM	8	1.02 ± 1.21	ND	ND	0.90 ± 1.12	0.93 ± 1.21
CYP2D6 PM	2	255.98 ± 21.65[week 1-4: -110, 122]	ND	ND	255.58 ± 82.96(week 4-5: -116, 115]	227.07 ± 63.04[week 1-5: -110, 122]	0.98
CYP2C9 EM	9	ND	1383.6 ± 616.89	ND	ND	1369.06 ± 398.2	0.98
CYP2C9 PM	1	ND	53.21	ND		141[week 1-5: -110, 122][week 2-5: -662, 670]
CYP2E1 (MR 2E1.1)	10	ND	ND	41306 ± 35123[week 3-4: -22397, 46003]	29503 ± 21450[week 4-5: -44310, 25867]	38724 ± 27430[week 3-5: -31618, 36782]	0.65
CYP2E1 (MR 2E1.2)	10	ND	ND	1.11 ± 0.37[week 3-4: -0.48, 0.58]	1.06 ± 0.53[week 4-5: -0.63, 0.42]	1.16 ± 0.47[week 3-5: -0.58, 0.47]	0.87
NAT2	10	ND	ND	0.49 ± 0.16[week 3-4: -0.20, 0.08]	0.55 ± 0.13[week 4-5: -0.12, 0.17]	0.52 ± 0.09[week 3-5: -0.18, 0.11]	0.56
CYP1A2	10	ND	ND	6.44 ± 2.96[week 3-4: -2.52, 2.77]	6.31 ± 1.79[week 4-5: -2.29, 3]	5.96 ± 2.04[week 3-5: -2.17, 3.13]	0.89
XO	10	ND	ND	0.56 ± 0.04[week 3-4: -0.03, 0.08]	0.53 ± 0.05[week 4-5: -0.07, 0.04]	0.55 ± 0.05[week 3-5: -0.05, 0.06]	0.5

^*Tukey adjustment for multiple comparisons, NAT2 = N-acetyltransferase 2, XO = xanthine oxidase, EM = extensive metabolizer, PM = poor metabolizer, ND = not done, P value is for the week effect, 3 drug = cocktail of caffeine, chlorzoxazone and dapsone, 4 drug = caffeine, chlorzoxazone, dapsone and metoprolol, 5 drug = caffeine, chlorzoxazone, dapsone, metoprolol and tolbutamide.