Table 1.

Statistical comparison of plasma pharmacokinetics of warfarin [R(+) and S(−)] enantiomers following the administration of a single oral dose of 30 mg warfarin alone (day 1, treatment A) and co-administered with multiple once daily doses of 100 mg anacetrapib (day 1, treatment B) in healthy adult subjects (n = 12 for treatment A and n = 11 for treatment B)

	Warfarin + anacetrapib			Warfarin alone			Warfarin + anacetrapib : warfarin alone
Pharmacokinetic parameter	n	GM	95% CI	n	GM	95% CI	GMR	90% CI	rMSE†
R(+) enantiomer
AUC(0–∞)‡ (µg ml−1 h)	11	95.55	(86.46, 105.61)	12	101.77	(92.16, 112.39)	0.94	(0.90, 0.97)	0.0480
Cmax‡ (µg ml−1)	11	1.54	(1.41, 1.68)	12	1.52	(1.39, 1.66)	1.01	(0.97, 1.05)	0.0520
tmax§ (h)	11	4.0	(2.0, 4.1)	12	4.0	(1.0, 4.0)
Apparent terminal t1/2¶ (h)	11	46.7	8.5	12	53.3	6.8
S(−) enantiomer
AUC(0–∞)‡ (µg ml−1 h)	11	58.14	(49.09, 68.85)	12	62.74	(53.04, 74.20)	0.93	(0.87, 0.98)	0.0781
Cmax‡ (µg ml−1)	11	1.51	(1.38, 1.65)	12	1.50	(1.37, 1.64)	1.01	(0.97, 1.05)	0.0513
tmax§ (h)	11	4.0	(1.0, 4.1)	12	4.0	(1.0, 4.0)
Apparent terminal t1/2¶ (h)	11	32.2	4.4	12	38.2	7.1

^†rMSE: Root mean square error on log scale. When multiplied by 100, provides estimate of the pooled within subject coefficient of variation.

^‡Back-transformed least squares mean and confidence interval from mixed effects model performed on natural log transformed values.

^§Median (min, max) reported for t_max.

^¶Harmonic mean (pseudo SD) reported for apparent terminal t_1/2. GM geometric mean, GMR geometric mean ratio.