Table B. Raltegravir Pharmacokinetic Parameters for Raltegravir-Naive and Raltegravir-Exposed Neonates

Body
PK Parameter  Initial Dose:
RAL 1.5 mg/kg Once Daily
RAL-Naive
(n = 25)d
Initial Dose:
RAL1.5 mg/kg Once Daily
RAL-Exposed
(n = 10)
Days 15–18:
RAL 3.0 mg/kg Twice Daily
RAL-Naive
(n = 24)e
Days 15–18:
RAL 3.0 mg/kg Twice Daily
RAL-Exposed
(n = 9)f
GM (CV%)     Target     GM (CV%)     Target     GM (CV%)     Target     GM (CV%)     Target    
AUC0-24h
(mg·h/L)a
38.2 (42.0%) Met: 13
Above: 11
Below: 0
42.9 (25.3%) Met: 4
Above: 6
Below: 0
      -------     ---------       --------       -------
 AUC0-12h
(mg·h/L)
     --------      --------        ---------  --------  14.3 (49.5%) Met: 14
Above: 8
Below: 1

 18.3 (62.8%)

Met: 3
Above: 5
Below: 1
Ctrough
(ng/mL)b
948 (84.0%) Above: 25
Below: 0
946 (74.0%) Met: 10
Above: 0
176 (162.1%) Above: 22
Below: 2
274 (176.4%) Above: 8
Below: 2
Cmax
(ng/mL)c
2,350 (36.5%) Below: 25
Above: 0
2,565.3 (23.1%) Met: 10
Above: 0
2,849 (47.5%) Below: 24
Above: 0
3,667 (46.3%) Met: 9
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
T½
(hours)
15.8 (101.4%) N/A 14.4 (69.5%) N/A 2.5 (34.1%) N/A 2.9 (20.1%) N/A
a AUC targets: AUC0-24h 12–40 mg·h/L and AUC0-12h 6–20 mg·h/L.
b Ctrough concentration >33 ng/mL. For initial dose, Clast collected at 24 hours was used. For Days 15 to 18, C12h was estimated when the 12 hours post-dose sample was collected earlier than 12 hours after dosing (the protocol specified a sample collection time of 8 to 12 hours post dose).
c Cmax <8,724 ng/mL.
AUC0-24h could not be estimated for one infant.
eAUC0-12h could not be estimated for one infant with delayed absorption.
f AUC0-12h and Cmax could not be estimated for one infant with incomplete sample collection.

Key: AUC = area under the curve; Clast = last measurable plasma concentration; Cmax = maximum concentration; Ctrough = trough concentration; CV = coefficient of variation; GM = geometric mean; PK = pharmacokinetic; RAL = raltegravir; T1/2 = half-life; Tmax = time to reach maximum concentration