Table 3.

Pharmacokinetic parameters for the pioglitazone metabolite M-III.

	Renal impairment
	Normal renal function (n = 6)	Moderate renal impairment (n = 9)			Severe renal impairment (n = 12)
	Mean ± s.d.	Mean ± s.d.	P-value†	% change vs normal renal function [CI]	Mean ± s.d.	P-value‡	% change vs normal renal function [CI]
Single dose
AUC0–∞ (µg.h l−1) (range)	15 071(9151–22 247)	8590(5447–12 780)	0.363	−43 [−94, 100]	13 394§(3238–539 408)	0.841	−11 [−74, 194]
Cmax (µg l−1)	183 ± 72	211 ± 66	0.409		136 ± 47	0.196
tmax (h) (range)	12.0(12.0–24.0)	10.0(8.0–16.0)			12.0(6.0–24.0)
t1/2 (h)	51.8 ± 13.2	25.6 ± 9.3			72.2 ± 77.7
Repeated doses
AUC0−24 (µg.h l−1) (range)	7289(4757–11 314)	6549(5178–8539)	0.527	−10 [−36, 26]	3991(2018–8810)	0.0009	−45 [−60, −25]
Cmax (µg l−1)	448 ± 157	381 ± 72	0.294		235 ± 95	0.0004*
tmax (h) (range)	11.0(2.0–48.0)	6.0(3.0–12.0)			5.0(3.0–16.0)
t1/2 (h)	29.1 ± 8.5	33.4 ± 21.4			24.0 ± 6.8

^†Normal renal function vs moderate renal impairment.

^‡Normal renal function vs severe renal impairment.

^*Statistically significant.

^§Includes one patient with a solitary unexplained high concentration at last sampling point. Mean value excluding this point is 8883 (range 3288-31 068). This patient was not an outlier on repeat dosing. Normal renal function: CL_CR>80 ml min⁻¹. Moderate renal impairment: CL_CR 30–60 ml min⁻¹. Severe renal impairment: CL_CR <30 ml min⁻¹.