Pharmacokinetics of orally administered omeprazole in children

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of or ally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, an d tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pa thological acid reflux on 34 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normal ized. Children remained on this dose for 3 months, and during this period t he pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional fur subjects and was perfo rmed in 25 of the 57 enrolled. The doses of omeprazole required were substa ntially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the rang es previously reported in adults. However, the plasma levels, area under th e plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (C-max), were lower in the younger age gro up, when the AUC and C-max were normalized to a dose of 1 mg/kg. Furthermor e, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a pe r kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children. (C) 2000 by Am. Cell. of Gas troenterology.