Table 3.

Cohort 2 Raltegravir Pharmacokinetic Parameters for Raltegravir-Naive and Raltegravir-Exposed Neonates

PK Parameter	Initial Dose: 1.5 mg/kg Once Daily RAL-Naive (N = 25)d		Initial Dose: 1.5 mg/kg Once Daily RAL-Exposed (N = 10)		Days 15–18: 3.0 mg/kg Twice Daily RAL-Naive (N = 24)e		Days 15–18: 3.0 mg/kg Twice Daily RAL-Exposed (N = 10)f
	Geometric Mean (CV%)	Target	Geometric Mean (CV%)	Target	Geometric Mean (CV%)	Target	Geometric Mean (CV%)	Target
AUC0–24h (mg*h/L)a	38.2 (42.0%)	Met: 13	42.9 (25.3%)	Met: 4	---------	-------------	---------	------------
		Above: 11		Above: 6
		Below: 0		Below: 0
AUC0–12h (mg*h/L)	-------	---------	---------	---------	14.3 (49.5%)	Met: 14	18.3 (62.8%)	Met: 3
						Above: 8		Above: 5
						Below: 1		Below: 1
Ctrough (ng/mL)b	948 (84.0%)	Met: 25	946 (74.0%)	Met: 10	176 (162.1%)	Met: 22	274 (176.4%)	Met: 8
		Below: 0		Below: 0		Below: 2		Below: 2
Cmax(ng/mL)c	2350 (36.5%)	Met: 25	2565 (23.1%)	Met: 10	2849 (47.5%)	Met: 24	3667 (46.3%)	Met: 9
		Above: 0		Above: 0		Above: 0		Above: 0
Tmax (hours)	5.4 (71.5%)	N/A	3.8 (88.8%)	N/A	2.3 (77.1%)	N/A	1.9 (52.3%)	N/A
T1/2 (hours)	15.8 (101.4%)	N/A	14.4 (69.5%)	N/A	2.5 (34.1%)	N/A	2.9 (20.7%)	N/A

^aAUC targets: AUC_0–24h 12–40 mg*h/L and AUC_0–12h 6–20 mg*h/L.

^bC_trough concentration >33 ng/mL. Note: For initial dose, Clast collected at 24 hours was used. For Days 15–18, C12 was estimated when the 12 hours post dose sample was collected earlier than 12 hours (protocol specified sample collection time of 8–12 hours post dose)

^cC_max <8724 ng/mL.

^dAUC_0–24h could not be estimated for one infant.

^eAUC_0–12h could not be estimated for one infant with delayed absorption.

^fAUC_0–12h and C_max could not be estimated for one infant with incomplete sample collection.

Key to Acronyms: AUC = area under the curve; C_max = maximum concentration; CV = coefficient of variation; PK = pharmacokinetic; RAL = raltegravir; T_1/2 = half-life; T_max = time to reach maximum concentration