Pharmacokinetics of stavudine and didanosine coadministered with nelfinavir in human immunodeficiency virus-exposed neonates

We evaluated the pharmacokinetics of stavudine (d4T) and didanosine (ddI) i n neonates. Eight neonates born to human immunodeficiency virus-infected mo thers were enrolled to receive 1 mg of d4T per kg of body weight twice dail y 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 2 8 days of age. For d4T, on days 14 and 28, the median areas under the conce ntration-time curves from 0 to 12 h (AUC(0-12)s) were 1,866 and 1,603, ng . 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(0-1 0)s were 1,573 and 1,562 h . ng/ml, respectively, and the median C(max)s we re 627 and 687 ng/ml, respectively. Systemic levels of exposure to d4T were comparable to those seen in children, suggesting that the pediatric dose o f 1 mg/kg twice daily is appropriate for neonates at 2 to 4 weeks of age. L evels of exposure to ddI were modestly higher than those seen in children. Whether this observation warrants a reduction of the ddI dose in neonates i s unclear.