Pharmacokinetics of antivirals in neonate.
BACKGROUND
About 1000 neonates with HIV infection are born every day worldwide. The antiviral therapy for newborn infants is a real necessity. Pharmacokinetics is an important contribution to therapy and no review has been published on the pharmacokinetics of antivirals in neonates up to now.


OBJECTIVE
This article provides a review on the pharmacokinetics of antivirals in the neonate. The pharmacokinetic parameters in the neonate are compared with those of the adult, and when possible, the pharmacokinetic parameters were compared in neonates of different ages.


RESULTS
Zidovudine is the antiviral with the largest amount of information on its pharmacokinetics. The clearance (Cl; l/h/kg) of zidovudine is 0.15 (premature), 0.34 (1 day), 0.69 (7 days), 0.65 (< or =14 days), 1.14 (>14 days) and 1.56 (adult). t(1/2) (h) of zidovudine is 7.2 (premature), 4.2 (1 day), 4.0 (7 days), 3.1 (< or =14 days), 1.9 (>14 days) and 1.1 (adult). Zidovudine is mainly eliminated by conjugation with glucuronic acid and glucuronosyl transferase develops postnatally. Cl of lamivudine is 0.19 (1 day), 0.32 (7 days) and 0.30 (adult) and the Cl (l/h/m2) of didanosine is 65 (1 day) and 271 (7 days). A greater volume of distribution (Vd) has been observed in the neonate compared with the adult for nelfinavir, nevirapine and pleconaril.


CONCLUSIONS
The pharmacokinetic parameters of antivirals differ in the neonate and in the adult. The Cl is reduced and t(1/2) is increased in the neonate compared with the adult for zidovudine, lamivudine and ganciclovir. t(max) is generally greater in the neonate than in the adult due to reduced absorption rate in the neonate. The Vd of nelfinavir, nevirapine and pleconaril is greater in the newborn than in the adult. The neonate is a developing organism and the pharmacokinetic parameters of antivirals vary during the first weeks of life.
Pacifici
Gian Maria
GM
Department of Neurosciences, Section of Pharmacology, Medical School, I-56126 Pisa, Italy. pacifici@biomed.unipi.it
D000998:Antiviral Agents / Q000493:pharmacokinetics*; D006801:Humans; D007231:Infant, Newborn; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics*
D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors