Clinical Pharmacology of Omeprazole in Infants and Children - Abstract
Omeprazole is a proton pump inhibitor it is a prodrug and requires activation in acid environments. After absorption into the systemic circulation, the prodrug diffuses into the parietal cells of the stomach and accumulates in the acidic secretory canaliculi. Here, it is activated by proton-catalysed formation of a tetracyclic sulfenamide trapping the drug so that it cannot diffuse back across the canalicular membrane. The activated form of omeprazole binds covalently with sulfhydryl groups of cysteine in the H+, K+-ATPase, irreversibly inactivating the pump molecule. Prescription of omeprazole is used to promote healing of gastric, duodenal ulcers, and to treat gastroesophageal reflux disease. Omeprazole is used to suppress gastric secretion when endoscopically-proven oesophagitis or peptic ulceration persists despite treatment with ranitidine and omeprazole is used in short-term treatment of duodenal reflux. In infants, the initial oral treatment consists in 0.7 mg/kg once-daily and the intravenous treatment consists in 0.5 mg/kg once-daily. In children, the dose of omeprazole varies with the child age or with child bodyweight. Omeprazole is extensively metabolised by CYP3A4 and CYP2C9 and the metabolites are omeprazole sulfone and 5-hydroxyomeprazole. The pharmacokinetics of omeprazole have been studied in infants and children and the elimination half-life is 56 and 58 min in infants and children respectively. Omeprazole interacts with drugs and poorly migrates into the breast-milk. The aim of this study is to review omeprazole dosing, pharmacokinetics, and treatments in infants and children and omeprazole metabolism and migration into breast-milk.