Omeprazole pharmacodynamics and gastric acid suppression in critically ill pediatric transplant patients

OBJECTIVE: To characterize the pharmacodynamics and pharmacokinetics of omeprazole suspension in critically ill pediatric liver/intestinal transplant patients. DESIGN: Open-label pharmacodynamic and pharmacokinetic study. SETTING: Pediatric intensive care unit of an academic medical center. PATIENTS: Eleven pediatric liver and/or intestinal transplant patients. INTERVENTIONS: Extemporaneously prepared 0.5 mg/kg omeprazole suspension every 12 hrs via nasogastric tube before sequential measurements of omeprazole serum concentration and gastric pH monitoring. Gastric pH was monitored continuously for 48 hrs and plasma omeprazole concentrations were determined upon first and multiple dosing. MEASUREMENTS AND MAIN RESULTS: Mean onset of action of omeprazole in a sodium bicarbonate vehicle was 62 +/- 82 mins (range, 2-226 mins). Subjects <4 yrs of age exhibited a more variable onset of omeprazole action (range, 3-226 mins) when compared with older subjects (onset of action, 2-40 min). Omeprazole maximum concentration and area under the concentration-time curve for the dosage interval were significantly greater upon multiple dosing when compared with the first dose. Mean baseline gastric pH in this study population was 1.0 +/- 0.8. Gastric pH remained >4.0 for 78.8% +/- 18.9% of the first dosage interval and 97.8% +/- 5.4% of multiple dosage intervals regardless of age when administered twice daily as a suspension. CONCLUSION: These results support the use of omeprazole administered twice daily as a suspension to maintain gastric pH of >4.0 and to achieve maximal pharmacodynamic effect in pediatric liver and/or intestinal transplant patients.