Related Experiment Videos
Single dose pharmacokinetics of pleconaril in neonates. Pediatric Pharmacology Research Unit Network
G L Kearns1, J S Bradley, R F Jacobs
1Department of Pediatrics, University of Missouri-Kansas City, MO, USA. gkearns@cmh.edu
Insights
Pleconaril is safe for neonates with suspected enteroviral infections. Pharmacokinetics in neonates differ from children, suggesting a 5.0-mg/kg dose every 8-12 hours may be appropriate.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Pleconaril is a broad-spectrum antipicornaviral agent.
- It has demonstrated activity against nonpolio enteroviruses.
Purpose of the Study:
- To evaluate the pharmacokinetics of pleconaril in neonates.
- To compare pleconaril pharmacokinetics between neonates and children.
Main Methods:
- 16 neonates received oral pleconaril (5 or 7.5 mg/kg).
- Plasma concentrations were measured over 24 hours.
- Pharmacokinetic parameters were determined and compared to data from children.
Main Results:
- Pleconaril was well-tolerated in all neonates.
- No significant pharmacokinetic differences were observed between the two doses in neonates.
- Neonates showed different volume of distribution and Cmax/AUC compared to children, but similar elimination half-life.
Conclusions:
- Age-dependent pharmacokinetic differences suggest higher bioavailability in older children/adults.
- A 5.0-mg/kg dose every 8-12 hours is proposed for future neonatal studies.
- Pleconaril shows promise for treating neonatal enteroviral infections.
Background:
Pleconaril is an orally active, broad spectrum antipicornaviral agent with activity against nonpolio enteroviruses. Pleconaril phamacokinetics was evaluated in 16 neonates (16.4 +/- 8.7 days postnatal age) with suspected enteroviral infection.
Methods:
Pleconaril (5 or 7.5 mg/kg) was administered orally to study subjects and plasma pleconaril concentrations quantified from serial blood samples obtained during 24 h after a single oral dose by gas chromatography with electrochemical detection. Pharmacokinetic parameter estimates were determined by noncompartmental methods and compared between doses and with similar 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 (Cmax 686.7 vs. 617.1 ng/ml), elimination half-life (t 1/2; 4.6 vs. 6.6 h), area under the plasma 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 correlation was observed between postconceptional age and AUC, V(dss)/F, t 1/2 or Cl/F for pleconaril. Comparison of pleconaril pharmacokinetics between neonates and children suggested a significant difference in V(dss)/F (9.3 vs. 4.7 liters/kg), dose-normalized Cmax, (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 between 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 drug in older children and adults than in neonates. Our data appear to support the use of a 5.0-mg/kg dose given every 8 to 12 h in future studies of pleconaril in neonatal patients with enteroviral infection.