C. Le Guellec, F. Odoul, A. Henrot, G. Paintaud, E. Saliba, M.-C. Saux, E. Autret-Leca
Department of pharmacology, Tours University Hospital, FRANCE
Background: Cisapride is used in neonates with gastro-oesophageal reflux. Nevertheless, only one pharmacokinetic study has been performed in this population. The aim of our study was to estimate pharmacokinetic parameters of cisapride in preterm and term neonates and their interindividual variability.
Methods: Neonates were administered cisapride orally 0.2 mg/kg four times a day. QT intervals were measured before and 48h after the first dose. Blood samples were drawn during an other biological control, at various times after dosing. Plasma concentrations of cisapride were measured using a validated HPLC method. Demographic and biological data and co-administered drugs were studied as possible covariates influencing cisapride pharmacokinetics. Data were analysed using NONMEM software with a one-compartment model.
Results: Ninety one subjects (45 girls and 46 boys), with gestational age: 26 – 37 weeks, birth weight: 750 – 2780 g and height: 32 – 50 cm were included. No side effect has been reported during the study. Plasma cisapride was measured in 250 samples (1 to 7 per subject) obtained from 2 to 123 days of life, between 10 min and 13.5 h after dosing. Cisapride concentrations ranged 5.5 – 172 ng/mL. Since too few samples were drawn early after dosing, the absorption constant was fixed to 2.5 h-1. Mean population clearance was 1.24 L/h and volume of distribution was 16.7 L (interindividual CV = 43.5 % and 17.2 %, respectively). Clearance was significantly related with weight and with both birth weight and postnatal age; interindividual CV of clearance and volume were 38 % and 36 %, respectively. No significant relationship was found between volume of distribution and any covariate.
Conclusion: As evidenced in our study, cisapride clearance in neonates is influenced by weight and data confirm that current recommendations of dosing on a weight-basis is not associated with unexpectedly high concentrations.
Reference: PAGE 12 () Abstr 383 [www.page-meeting.org/?abstract=383]
Poster: poster