Table 3.

Pharmacokinetic variables for tizanidine metabolites 3, 4 and 5 during the placebo and rofecoxib (25 mg day⁻¹) phases in nine healthy subjects

Variable	Placebo phase (control)	Rofecoxib phase	95% CI	P-value
Metabolite 3
Cmax (U ml−1)	0.45 ± 0.11	0.38 ± 0.81		0.14
Relative to control (range)		0.84 (0.50–1.50)	0.53, 1.11
tmax (min)	90 (60, 180)	300 (180, 1400)		0.003
t1/2 (h)*	4.3 ± 1.5	17.5 ± 8.1		0.002
Relative to control (range)		4.40 (2.90–6.80)	2.56, 5.65
AUC0–24 (U h ml−1)	3.1 ± 1.1	6.4 ± 1.4		<0.001
Relative to control (range)		2.06 (1.40–3.90)	1.77, 2.32
AUC0–∞ (U h ml−1)*	3.0 ± 1.3	12.3 ± 9.1		0.011
Relative to control (range)		4.10 (2.70–8.60)	1.73, 6.47
Metabolite 4
Cmax (U ml−1)	1.3 ± 0.1	0.64 ± 0.13		<0.001
Relative to control (range)		0.51 (0.38–0.70)	0.42, 0.64
tmax (min)	60 (40, 240)	300 (240, 420)		0.003
t1/2 (h)	4.7 ± 0.7	8.0 ± 4.0		0.016
Relative to control (range)		1.60 (1.20–2.80)	1.15, 2.23
AUC0–24 (U h ml−1)	10.0 ± 1.3	7.4 ± 1.1		<0.001
Relative to control (range)		0.75 (0.59–0.86)	0.65, 0.85
AUC0–∞ (U h ml−1)	10.4 ± 1.6	9.1 ± 3.2		0.16
Relative to control (range)		0.87 (0.69–1.40)	0.71, 1.05
Metabolite 5
Cmax (U ml−1)	0.10 ± 0 06	0.17 ± 0.07		0.09
Relative to control (range)		1.70 (0.22–5.60)	0.9, 2.5
tmax (min)	60 (40, 240)	180 (60, 420)		0.046

Data are mean ± SD or mean with 95% CI; t_max data are given as median with range. CI, Confidence interval; C_max, maximum plasma concentration; t_max, time to reach C_max; t_1/2, half-life; AUC₀₋₂₄, area under plasma concentration–time curve from time 0–24 h; AUC_0–∞, area under plasma concentration–time curve from time 0 to infinity.

^*Data from eight subjects only are shown, because the t_1/2 and AUC_0–∞ could not be determined for subject 8 (the individual with the lowest CYP1A2 activity), because M-3 concentration was rising up to the last time point (24 h).