Clinical Pharmacology of Lansoprazole in Infants and Children - Abstract
Lansoprazole is a proton pump inhibitor and is a prodrug. 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 then binds covalently with sulfhydryl groups of cysteine in the H+, K+-ATPase irreversibly inactivating the pump molecule. Acid secretion resumes only after new pump molecules are synthesized and inserted into the luminal membrane, providing a prodrug (up to 24 to 48 hours) suppression of acid secretion, despite the much shorter plasma elimination half-life of about 0.5 to 3 hours of the parent compound. Lansoprazole is used to promote healing of gastric and duodenal ulcers, and to treat gastroesophageal reflux disease, including erosive esophagitis. In newborns, the oral lansoprazole is 0.2 to 0.3 mg/kg once-daily, and in children, lansoprazole dose varies with the child bodyweight. Lansoprazole has been found efficacy and safe in infants and children. Lansoprazole is converted into hydroxy lansoprazole by CYP2C19 and into lansoprazole sulfone by CYP3A4. The elimination half-life is less than 1 hour in infants and children. The treatment of infants and children with lansoprazole has been extensively studied and lansoprazole interacts with drugs. The aim of this study is to review lansoprazole dosing, efficacy and safety, pharmacokinetics, and the treatment in infants and children, and lansoprazole metabolism and interaction with drugs.