Intravenous omeprazole in children: Pharmacokinetics and effect on 24-hourintragastric pH

Background: Omeprazole is a proton pump inhibitor, acting selectively on th e gastric parietal cell H+K+-adenosine triphosphatase. Data on the intraven ous route are limited in children and not available in infants. Objective: This study was designed to determine the pharmacokinetics and th e optimal dosage of intravenous omeprazole in patients younger than 30 mont hs of age. Methods: Nine children (three girls), aged 4.5 to 27 months, with normal li ver and renal functions requiring intravenous omeprazole were studied. Afte r enrollment in the study and randomization, omeprazole was administered on ce daily, at 8 AM, as a 1-hour infusion. Group 1, consisting of the first f our patients. received 20 mg/1.73 m(2), and group 2, consisting of the foll owing five patients, received 40 mg/1.73 m(2). At day 3, a 24-hour intragas tric pH and a pharmacokinetic study of omeprazole were performed. Plasma co ncentrations were measured by high-performance liquid chromatography. Results: Patients in group 2 had a significantly higher median pH (6.99 vs. 3.35: P = 0.01) and percent of monitored time with gastric pH >4 than chil dren given 20 mg/1.73 m(2) (90.6% vs. 44.8%; P < 0.01). Four had a pH more than 4 during more than 90% of the time versus none of the patients of grou p 1. The plasma concentration versus time curves showed rapid elimination o f the drug. The median area under the curve of omeprazole was 0.78 <mu>g . mL(-1) . h(-1) (range, 0.55-1.64 mug . mL(-1) . h(-1)) and 3.95 mug . mL(-1 ) . h(-1) (range, 1.9-4.9 mug . mL(-1) . h(-1)). respectively, in groups 1 and 2 (P < 0.05). Systemic clearance was not different between the two grou ps: median values were 0.68 and 0.42 L <bullet> kg(-1) . h(-1) (P = 0.22). Conclusions: In critical situations, intravenous administration of omeprazo le may be required in infants. The authors demonstrate that the dose of 20 mg/1.73 m(2) is not effective in maintaining 24-hour gastric pH of more tha n 4 and that a dose of 40 mg/1.73 m(2) is required.