Table 3.

Pharmacokinetic relationships

Pharmacokinetic variables (250 mg dose levels)	Non-EIAD (n = 6)	EIAED (n = 13)	P
Temsirolimus
t1/2 (h)	8.83 (±2.71)	9.38 (±2.16)	0.64
Cmax (μg/mL)	2.36 (±1.64)	1.45 (±0.89)	0.13
AUC (μg × h/mL)	5.03 (±2.92)	3.32 (±0.84)	0.06
CL (L/h)	66.15 (±41.69)	79.60 (±18.61)	0.34
Vdss (L)	470 (±362)	699 (±241)	0.12
Sirolimus
t1/2 (h)	51.35 (±24.43)	28.86 (±13.55)	0.02
Cmax (ng/mL)	260.60 (±125)	131.83 (±46.37)	0.004
AUC (μg × h/mL)	14.49 (±4.94)	6.82 (±3.28)	0.008
AUCsum (μg × h/mL)	19.52 (±6.65)	9.74 (±3.67)	0.006
AUCratio	3.37 (±1.27)	2.12 (±0.93)	0.002

Population pharmacokinetic variables	Non-EIAD (n = 19)	EIAED (n = 17)	P
Temsirolimus
t1/2 (h)	9.48 (±2.93)	9.57 (±2.25)	0.92
Cmax (μg/mL/mg)*	0.012 (±0.013)	0.010 (±0.01)	0.41
AUC (μg × h/mL/mg)*	0.02 (±0.009)	0.01 (±0.004)	0.002
CL (L/h)	57.82 (±26.76)	83.10 (±18.86)	0.003
Vdss (L)	513 (±290)	689 (±276)	0.07
Sirolimus
t1/2 (h)	42.04 (±49.42)	27.45 (±10.98)	0.24
Cmax (ng/mL/mg)*	1.08 (±0.50)	0.58 (±0.24)	0.0007
AUC (μg × h/mL/mg)*	0.062 (±0.03)	0.027 (±0.01)	0.00006
AUCratio	3.50 (±1.99)	2.18 (±0.93)	0.018

^*Dose normalized.