title: Population pharmacokinetics of domperidone in preterm neonates.
abstract: OBJECTIVE
  A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population.
  
  
  METHODS
  An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plasma concentration was measured by high-performance liquid chromatography (HPLC) assay, and a one-compartment model with first-order absorption was fitted to the data using NONMEM version V level 1.1.
  
  
  RESULTS
  The mean peak and trough plasma concentration values of domperidone were, respectively, 25.3 +/- 20.5 ng/ml and 15.4 +/- 11.4 ng/ml (mean +/- standard deviation). The pharmacokinetic parameters (interindividual variability%) were clearance (Cl/F) = 0.92 L/h (51.6%), volume of distribution (Vd/F) = 0.405 L (68%), and absorption constant rate (Ka) = 0.0843 h(-1) (55.8%). The clearance is not lower than values reported in adults. No influence of covariates (postnatal age, prematurity, weight, gender) on domperidone pharmacokinetic parameters was found.
  
  
  CONCLUSIONS
  This pilot study designed with a limited sampling strategy showed that domperidone plasma concentrations were consistent with those reported in adults, suggesting that domperidone dosage regimen currently used in preterm neonates is suitable.
authors.affiliation: Clinical Pharmacology Department, CHU de Nantes, Nantes, France. eric.dailly@chu-nantes.fr
authors.forename: E
authors.initials: E
authors.lastname: Dailly
authors.forename: M H
authors.initials: MH
authors.lastname: Drouineau
authors.forename: V
authors.initials: V
authors.lastname: Gournay
authors.forename: J C
authors.initials: JC
authors.lastname: Rozé
authors.forename: P
authors.initials: P
authors.lastname: Jolliet
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001724:Birth Weight; D004294:Domperidone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010865:Pilot Projects; D011237:Predictive Value of Tests
chemical_list: D000932:Antiemetics; D004294:Domperidone