Intestinal metabolism and transport of drugs in children: the effects of age and disease.
The presence of cytochrome P450 enzymes in the small bowel results in the reduced bioavailability of several drugs. Recently, there has been much research on the interplay between these enzymes and transporter proteins such as P-glycoprotein. Intestinal drug metabolism not only has an effect on drug disposition but also may have a role in protecting the host from xenobiotics. Although there is some information on how both the enzymes and transporters develop in the small bowel with age, there is little information regarding the clinical effects of these changes. In addition to developmental changes, the influence of gastrointestinal disease and nutrition are additional covariates in the intestinal metabolism of drugs.
Johnson
Trevor N
TN
Pharmacy Department, Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK. t.johnson@simcyp.com
Thomson
Mike
M
D000375:Aging / Q000378:metabolism*; D001682:Biological Availability; D002648:Child; D016572:Cyclosporine / Q000378:metabolism / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005772:Gastrointestinal Transit / Q000502:physiology*; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008874:Midazolam / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D008874:Midazolam