Proton pump inhibitors in pediatrics: relevant pharmacokinetics and pharmacodynamics.
A marked discordance between the disposition of proton pump inhibitors (PPIs) in plasma and the kinetics of effect suggests the need for new approaches to characterize the clinical pharmacology of PPIs in infants and children. An assessment of pharmacokinetics and pharmacodynamics must take into account the genetic polymorphism of CYP2C19 and the impact of ontogeny on the activity of this and other enzymes (e.g., CYP3A4) which affect the biotransformation of the PPIs and, thus, their plasma clearance. In addition, the potential effects of extemporaneous formulations of the drugs on their rate and extent of absorption must be considered. Because of the apparent safety of PPIs and a well-demonstrated dose-response-effect relationship in adults, pediatric pharmacokinetic data and an exposure correlate, such as the dose-area-under-the-plasma-concentration-versus-time-curve relationship, can be used as a bridge to determine pediatric dosing.
Kearns
Gregory L
GL
University of Missouri-Kansas City, and Chief, Division of Pediatric Pharmacology and Medical Toxicology, Children's Mercy Hospitals and Clinics, Kansas, City Missouri, U.S.A. gkearns@cmh.edu
Winter
Harland S
HS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007408:Intestinal Absorption; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077402:Pantoprazole; D011110:Polymorphism, Genetic; D054328:Proton Pump Inhibitors; D012449:Safety; D013454:Sulfoxides / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D003577:Cytochrome P-450 Enzyme System; D000077402:Pantoprazole; D009853:Omeprazole