Population pharmacokinetics of domperidone in preterm neonates.
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.
Dailly
E
E
Clinical Pharmacology Department, CHU de Nantes, Nantes, France. eric.dailly@chu-nantes.fr
Drouineau
M H
MH
Gournay
V
V
Rozé
J C
JC
Jolliet
P
P
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
D000932:Antiemetics; D004294:Domperidone