The pharmacokinetics and pharmacodynamics of metoclopramide oral solution were evaluated in six infants (0.9-5.4 months) with gastroesophageal reflux (GER) following the initial and 10th dose of 0.15 mg/kg administered every 6 h. Metoclopramide pharmacodynamics were assessed by pre- and post-dose comparison of esophageal pH monitoring data and clinical evaluation of improvement in GER symptoms. A significant reduction in the number of episodes of pH less than 4 for greater than 5 min and the longest episode of GER was seen between the predose and 10th dose (steady-state) evaluation periods. Four of the 6 patients had a 75% reduction in reflux time and demonstrated improvement in clinical symptoms by the 10th dose. Metoclopramide pharmacokinetics were best characterized by a one-compartment open model following the first and 10th doses. Metoclopramide serum concentrations (mean +/- SD) ranged from 56.2 +/- 23.5 to 32.7 +/- 13.2 ng/ml within a 6-h dosing interval at steady state. There were no significant differences between the first versus tenth dose values for Tmax (2.0 +/- 0.5 versus 2.2 +/- 0.4 h), Kel (0.14 +/- 0.03 versus 0.17 +/- 0.04 h-1), Vdarea (4.9 +/- 0.4 versus 4.4 +/- 0.6 L/kg), or clearance (0.66 +/- 0.16 versus 0.67 +/- 0.13 L/h/kg). The youngest subject (3.5 weeks) had a metoclopramide t 1/2 of 23.1 h following initial dose, which decreased to 10.3 h at steady-state. Care should be exercised in using the 0.15 mg/kg dose in infants less than 1 month of age as prolonged clearance may produce excessive serum concentrations.