Population pharmacokinetics of domperidone in preterm neonates

• Published in: European journal of clinical pharmacology 2008-12, Vol.64 (12), p.1197-1200
• Main Authors: Dailly, E, Drouineau, M. H, Gournay, V, Rozé, J. C, Jolliet, P
• Format: Article
• Language: English
• Subjects: Antiemetics - administration & dosage; Antiemetics - blood; Antiemetics - pharmacokinetics; Antiemetics - therapeutic use; Babies; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Birth Weight; Domperidone; Domperidone - administration & dosage; Domperidone - blood; Domperidone - pharmacokinetics; Domperidone - therapeutic use; Drug therapy; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature - blood; Infant, Premature - metabolism; Male; Medical sciences; Metabolic Clearance Rate; Models, Biological; Neonatal care; Pharmacokinetics and Disposition; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pilot Projects; Population pharmacokinetics; Predictive Value of Tests; Premature birth; Prescription drugs; Preterm neonates
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-008-0535-1

Purpose 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. Conclusion 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.