Cisapride is used in preterm infants with gastroesophageal reflux; however, neither its disposition nor its efficacy have been reported. We evaluated cisapride disposition in 7 infants (BW: 760-1095, 28-33 wks postconceptional age). Six plasma samples (200 μl) were obtained during the 24 hours after a single 0.2 mg/kg oral gavage dose. Dosing was 15 min prior to feeding. Cisapride concentrations were determined using LC/MS/MS (min detection: 1 ng/ml). Cisapride peak concentrations varied 26 fold (3-83 ng/ml). In 2 patients, all concentrations were low (<10 ng/ml). In the other 5 patients, peak values were comparable to those reported in adults given a single 10 mg oral dose. However, in 4 of these 5 patients, the time to peak concentration was late, occurring at 6 hrs or later. Two of the 4 patients with delayed peak concentrations had evidence of severe reflux after dosing. In the 5 patients whose cisapride concentrations fell during the study period, the area under the concentration time curve varied 8 fold (73 - 608 ng/ml/h), and the terminal half life varied about 3 fold (4.1-11.9 h). Our data demonstrate a marked intersubject variation in cisapride disposition in this patient population. We speculate that the observed diminished and delayed absorption may decrease efficacy in preterm infants with GE reflux. Proof of efficacy and optimal cisapride dosing is still needed for this indication in this patient population.Analytical support for this project was provided by Janssen Pharmaceutica.