期刊
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
卷 4, 期 8, 页码 1065-1074出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425255.4.8.1065
关键词
chronic renal failure; CYP; cytochrome P450; drug transport; efflux transporters; hepatic clearance; P-glycoprotein; uremic toxins
资金
- Intramural NIH HHS [Z99 CL999999] Funding Source: Medline
Background: Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine. Objectives: The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport. Methods: A search of the National Library of Medicine PubMed was done with terms such as chronic renal failure, cytochrome P450 [CYP], liver metabolism, efflux drug transport and uptake transport, including relevant articles back to 1969. Results: Animal studies in CRF have shown a significant downregulation (40-85%) of hepatic and intestinal CYP metabolism. High levels of parathyroid hormone, cytokines and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein and organic anion transporting polypeptide are also affected. Conclusion: CRF alters intestinal, renal and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions.
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