Single dose pharmacokinetics of pleconaril in neonates

Background. Pleconaril is an orally active, broad spectrum antipicornaviral agent with activity against nonpolio enteroviruses. Pleconaril phamacokine tics was evaluated in 16 neonates (16.4 +/- 8.7 days postnatal age) with su spected enteroviral infection, Methods, Pleconaril (5 or 7.5 mg/kg) was administered orally to study subje cts and plasma pleconaril concentrations quantified from serial blood sampl es obtained during 24 h after a single oral dose by gas chromatography with electrochemical detection. Pharmacokinetic parameter estimates were determ ined by noncompartmental methods and compared between doses and with simila r data obtained from a previous study of pleconaril disposition in children (n = 18, 2 to 12 years). Results. Pleconaril was well-tolerated in all neonates without discernible adverse events. Comparison between the 5.0- and 7.5-mg/kg doses revealed no significant differences in peak plasma concentration (C-max 686.7 vs. 617. 1 ng/ml), elimination half-life (t(1/2); 4.6 us. 6.6 h), area under the pla sma concentration vs. time curve (AUC; 5162.6 vs. 5523.9 ng/ml/h), apparent steady state volume of distribution (V-dss/F; 9.3 vs. 17.1 liters/ kg) and apparent oral clearance (Cl/F; 1.3 vs. 1.7 liters/h/kg), In addition, no c orrelation was observed between postconceptional age and AUG, V-dss/F, t(1/ 2) or Cl/F for pleconaril, Comparison of pleconaril pharmacokinetics betwee n neonates and children suggested a significant difference in V-dss/F (9.3 vs, 4.7 liters/kg), dose-normalized C-max (686.7 vs. 1272.5 ng/ml) and AUC (5125.6 vs. 8131.2 ng/ml/h). In contrast, the mean elimination t(1/2) betwe en neonates and children was not appreciably different. Conclusions. The apparent age-dependent differences in the pharmacokinetics of pleconaril may in part be related to increased bioavailability of the d rug in older children and adults than in neonates, Our data appear to suppo rt the use of a 5.0-mg/kg dose given every 8 to 12 h in future studies of p leconaril in neonatal patients with enteroviral infection.