Pharmacokinetics of metoclopramide in neonates.
Despite its wide use as a prokinetic agent in neonates and infants with gastroesophageal reflux (GER), the pharmacokinetics of metoclopramide have not been characterized in this pediatric subpopulation. A single-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 quantitated from repeated blood samples (n = 9 over 24 hours) by high-performance liquid chromatography. A one-compartment open model with first-order absorption best described the plasma concentration-time data. No correlations were observed between gestational, postnatal, or postconceptional age and any of the pharmacokinetic parameters studied. Comparison of the pharmacokinetic parameters from the study cohort and those reported previously from a similar study of older infants revealed no statistically significant differences. However, a prolonged apparent plasma clearance (Cl/F) of metoclopramide was observed in 30% of the infants studied, and the mean Cl/F and apparent steady-state volume of distribution (Vdss/F) were approximately 1.4- and 2.1-fold higher, respectively, than values reported in previous studies of metoclopramide disposition in adults. These data suggest that metoclopramide pharmacokinetics may exhibit a developmental dependency. Thus, a metoclopramide dose of 0.15 mg/kg given orally every 6 hours is recommended for the initiation of prokinetic therapy with this agent in infants who are < or = 31 weeks postconceptional age.
Kearns
G L
GL
Department of Pediatrics, University of Missouri-Kansas City, MO 64108, USA.
van den Anker
J N
JN
Reed
M D
MD
Blumer
J L
JL
D000284:Administration, Oral; D000367:Age Factors; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005764:Gastroesophageal Reflux / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007234:Infant, Premature / Q000378:metabolism; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000932:Antiemetics; D008787:Metoclopramide