PHARMACOKINETICS OF METOCLOPRAMIDE IN NEONATES

Despite its wide use as a prokinetic agent in neonates and infants wit h gastroesophageal reflux (GER), the pharmacokinetics of metoclopramid e have not been characterized in this pediatric subpopulation. A singl e-dose pharmacokinetic study of oral metoclopramide (0.1 to 0.15 mg/kg ) was performed in 10 fasted premature infants (weight 1.1 to 3.2 kg) ranging from 31 to 40 weeks postconceptional age. Metoclopramide was q uantitated from repeated blood samples (n = 9 over 24 hours) by high-p erformance liquid chromatography. A one-compartment open model with fi rst-order absorption best described the plasma concentration-time data . No correlations were observed between gestational, postnatal, or pos tconceptional age and any of the pharmacokinetic parameters studied. C omparison of the pharmacokinetic parameters from the study cohort and those reported previously from a similar study of older infants reveal ed no statistically significant differences. However, a prolonged appa rent plasma clearance (Cl/F) of metoclopramide was observed in 30% of the infants studied, and the mean Cl/F and apparent steady-state volum e of distribution (Vd(ss)/F) were approximately 1.4- and 2.1-fold high er, respectively, than values reported in previous studies of metoclop ramide disposition in adults. These data suggest that metoclopramide p harmacokinetics may exhibit a developmental dependency. Thus, a metocl opramide dose of 0.15 mg/kg given orally every 6 hours is recommended for the initiation of prokinetic therapy with this agent in infants wh o are less than or equal to 31 weeks postconceptional age.