Table 2.

Nontransformed Pharmacokinetic Parameters for Istradefylline and its M1 and M8 Metabolites Following Oral Administration of a Single Dose of Istradefylline 40 mg Alone or in Combination With Steady‐State Rifampin 600 mg/day in Healthy Subjects

Pharmacokinetic Parametera	Istradefylline (n = 20)	Istradefylline + Rifampin (n = 20)
Istradefylline
Cmax, ng/mL	181.1 (68.6)	97.8 (24.4)
Tmax, h	2.0 (1.0, 12.0)	1.9 (1.0, 6.0)
AUClast, ng·h/mL	9854 (2853)	2037 (513)
AUCinf, ng·h/mL	11 100 (3388)	2096 (514)
t1/2, h	94.8 (36.5)	31.5 (8.6)
Vz/F, L	515 (188)	925 (336)
CL/F, L/h	4.0 (1.5)	20.6 (6.7)
M1 metabolite
Cmax, ng/mL	4.34 (2.49)	7.25 (2.27)
Tmax, h	3.5 (2.0, 12.0)	3.0 (1.0, 6.0)
AUClast, ng·h/mL	123 (77.6)	118 (44.3)
AUCinf, ng·h/mL	na	159 (47.6)b
t1/2, h	na	17.6 (4.95)b
M/P ratio (Cmax)	0.0241 (0.0045)	0.0778 (0.0161)
M/P ratio (AUClast)	0.0134 (0.0078)	0.0613 (0.0195)
M/P ratio (AUCinf)	na	0.0821 (0.0138)b
M8 metabolite
Cmax, ng/mL	12.6 (5.13)	14.1 (4.27)
Tmax, h	3.0 (2.0, 24.0)	3.0 (1.0, 6.0)
AUClast, ng·h/mL	484 (202)	146 (36.9)
AUCinf, ng·h/mL	610 (272)c	170 (34.8)d
t1/2, h	62.0 (33.0)c	10.8 (4.66)d
M/p ratio (Cmax)	0.0674 (0.0131)	0.1377 (0.0199)
M/P ratio (AUClast)	0.0461 (0.0104)	0.0705 (0.0145)
M/P ratio (AUCinf)	0.0513 (0.0093)c	0.0785 (0.0134)d

AUC_inf, area under the plasma concentration–time curve (AUC) from time zero to infinity; AUC_last, AUC from time zero to the last quantifiable concentration; CL/F, apparent clearance; C_max, observed maximum plasma concentration; M/P ratio, metabolite‐to‐parent ratio for pharmacokinetic exposure; na, not applicable; T_max time to reach C_max; t_1/2, terminal elimination half‐life; V_z/F, apparent volume of distribution.

^aData are shown as arithmetic mean (standard deviation) except for T_max values, which are presented as median (min, max).

^bn = 13.

^cn = 14.

^dn = 19.