Pharmacokinetics and pharmacodynamics of ranitidine in neonates treated with extracorporeal membrane oxygenation

Abstract

The pharmacokinetics and pharmacodynamics of ranitidine were studied in 13 term neonates with stable renal and hepatic function who were treated with extracorporeal membrane oxygenation (ECMO). Ranitidine was initially administered as a single 2 mg/kg dose over 10 minutes and intragastric pH was monitored to determine response. Within 90 minutes after administration of ranitidine, intragastric pH for all of the patients whose initial reading was < or = 4 had increased to > 5. Intragastric pH remained > 4 for a minimum of 15 hours. Mean +/- 1 standard deviation elimination half-life was 6.61 +/- 2.75 hours, and 41.5 +/- 22.2% of the single dose was eliminated in urine within 24 hours. Total plasma clearance of ranitidine correlated well with estimated glomerular filtration rate. Twenty-four hours after the initial dose, a continuous infusion of ranitidine (2 mg/kg/24 hr) was started and continued for 72 hours or until ECMO was discontinued. Eleven patients completed 48 hours of continuous infusion and seven completed all 72 hours. Plasma clearance and elimination half-life were determined from steady-state plasma ranitidine concentrations 24, 48, and 72 hours after the start of the infusion. There were no significant differences in clearance between these intervals. These data suggest that for term neonates with stable renal and hepatic function, ranitidine does not need to be administered more frequently than every 12 hours. A continuous infusion of 2 mg/kg/24 hours maintained intragastric pH above 4 in more than 90% of our patients, and in our opinion is the preferred method for delivering ranitidine to term neonates undergoing ECMO who require H2 antagonists. Response to therapy should be monitored by repeated measurement of gastric pH and the dose should be adjusted accordingly.