Table 4. Pharmacokinetic parameters for blood concentrations of ridaforolimus on day 5 of oral dosing (once daily × 5 days per week) according to dose level in pediatric patients.

Pharmacokinetic parameter	Dose level 1 22 mg/m2 (n = 4)	Dose level 2 28 mg/m2 (n = 3)	Dose level 3 33 mg/m2 (n = 12)a
Day 5 AUC0–24h, h•ng/mL	n = 4	n = 3	n = 11
Geometric mean (CV%b)	1,340 (32)	2,330 (36)	2,280 (30)
C4h, ng/mL	n = 4	n = 3	n = 11
Arithmetic mean (SD)	139 (57)	228 (21)	200 (81)
Geometric mean (CV%b)	131 (41)	227 (10)	184 (45)
C8h, ng/mL	n = 4	n = 3	n = 12
Arithmetic mean (SD)	74 (23)	119 (35)	118 (39)
Geometric mean (CV%b)	71 (37)	116 (32)	113 (32)
t1/2, h	n = 3c	n = 3	n = 9
Arithmetic mean (SD)	25.5 (2.8)	28.2 (9.5)	26.9 (8.7)
Median (range)	24.5 (23.5–28.7)	26.5 (19.7–38.4)	24.9 (21.0–49.1)
Geometric mean (CV%b)	25.5 (10.5)	27.2 (34.5)	26.0 (26.7)

^aThirteen patients were enrolled with daily dose administration of ridaforolimus 33 mg/m²; 1 patient was excluded because of no exposure on day 5. For 1 patient, AUC, C_4h, and t_1/2 were not evaluable because of limited sampling. For 2 additional patients, t_1/2 was not evaluable. The geometric mean of BSADN AUC (n = 11) was 69.8 h•ng•m²/(mL•mg). The lower bounds of the 90% 1-sided confidence intervals for the geometric means of day 5 AUC_0–24h, C_4h, C_8h, BSADN AUC, and t_1/2 were 2,020 h•ng/mL, 154 ng/mL, 100 ng/mL, 61.2 h•ng•m²/(mL•mg), and 23.0 h, respectively. Backtransformed least-squares mean and confidence interval were performed on natural log-transformed values.

^bGeometric coefficient of variation, where CV% = 100 × √(exp [S²] − 1) and S² is the observed variance on the natural logarithmic scale.

^cFor 1 patient, t_1/2 was not evaluable.

BSADN AUC, area under the concentration-versus-time curve normalized by BSA-adjusted dose; C_4h, concentration at 4 hours; C_8h, concentration at 8 hours; CV%, coefficient of variation as a percentage; t_1/2, elimination half-life.