Pharmacokinetics of stavudine and didanosine coadministered with nelfinavir in human immunodeficiency virus-exposed neonates.
We evaluated the pharmacokinetics of stavudine (d4T) and didanosine (ddI) in neonates. Eight neonates born to human immunodeficiency virus-infected mothers were enrolled to receive 1 mg of d4T per kg of body weight twice daily and 100 mg of ddI per m(2) once daily in combination with nelfinavir for 4 weeks after birth. Pharmacokinetic evaluations were performed at 14 and 28 days of age. For d4T, on days 14 and 28, the median areas under the concentration-time curves from 0 to 12 h (AUC(0-12)s) were 1,866 and 1,603, ng x h/ml, respectively, and the median peak concentrations (C(max)s) were 463 and 507 ng/ml, respectively. For ddI, on days 14 and 28, the median AUC(0-10)s were 1,573 and 1,562 h x ng/ml, respectively, and the median C(max)s were 627 and 687 ng/ml, respectively. Systemic levels of exposure to d4T were comparable to those seen in children, suggesting that the pediatric dose of 1 mg/kg twice daily is appropriate for neonates at 2 to 4 weeks of age. Levels of exposure to ddI were modestly higher than those seen in children. Whether this observation warrants a reduction of the ddI dose in neonates is unclear.
Rongkavilit
C
C
HIV Netherlands-Australia-Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. crongkav@dmc.org
Thaithumyanon
P
P
Chuenyam
T
T
Damle
B D
BD
Limpongsanurak
S
S
Boonrod
C
C
Srigritsanapol
A
A
Hassink
E A
EA
Hoetelmans
R M
RM
Cooper
D A
DA
Lange
J M
JM
Ruxrungtham
K
K
Phanuphak
P
P
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004279:DNA, Viral / Q000737:chemistry; D016049:Didanosine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019888:Nelfinavir / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018119:Stavudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine