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.