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Colon-specific delivery of celecoxib is a potential strategy to improve toxicological and pharmacological properties of the selective Cox-2 inhibitor: implication in treatment of familiar adenomatous polyposis.
J Drug Target. 2012 Jul; 20(6):524-34.JD

Abstract

In general, colon-specific delivery of a drug decreases systemic absorption and increases therapeutic concentration of the drug at the target site. N-succinylglutam-1 or 5-yl celecoxib (SG1C and SG5C) were prepared as a colon-specific prodrug of celecoxib, a selective Cox-2 inhibitor, and investigated whether the celecoxib derivatives could deliver celecoxib to the target site and improve cardiovascular toxicity and therapeutic effectiveness for the treatment of familiar adenomatous polyposis. SG1C and SA5C were cleaved to release celecoxib in the cecal contents while stable in small intestinal contents. The cecal release of celecoxib was much greater for SG1C than SG5C. SG1C administered orally was barely detected in the blood and urine. SG1C delivered much greater amount of celecoxib to the large intestine while keeping the plasma concentration of celecoxib at much lower level compared with oral administration of free celecoxib. Consistent with these pharmacokinetic results, SG1C supplied a greater concentration of celecoxib for the entire colonic tissue and did not change the serum level of 6-keto-PGF(1α) whose decrease is associated with the cardiovascular toxicity of celecoxib. Taken together, colon-specific delivery of celecoxib using a prodrug approach may be a useful strategy to improve toxicological and pharmacological properties of celecoxib.

Authors+Show Affiliations

Laboratory of Biomedicinal Chemistry, College of Pharmacy, Pusan National University, Busan, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22632102

Citation

Lee, Yonghyun, et al. "Colon-specific Delivery of Celecoxib Is a Potential Strategy to Improve Toxicological and Pharmacological Properties of the Selective Cox-2 Inhibitor: Implication in Treatment of Familiar Adenomatous Polyposis." Journal of Drug Targeting, vol. 20, no. 6, 2012, pp. 524-34.
Lee Y, Kim H, Kim W, et al. Colon-specific delivery of celecoxib is a potential strategy to improve toxicological and pharmacological properties of the selective Cox-2 inhibitor: implication in treatment of familiar adenomatous polyposis. J Drug Target. 2012;20(6):524-34.
Lee, Y., Kim, H., Kim, W., Yoon, J. H., Jeong, S. H., & Jung, Y. (2012). Colon-specific delivery of celecoxib is a potential strategy to improve toxicological and pharmacological properties of the selective Cox-2 inhibitor: implication in treatment of familiar adenomatous polyposis. Journal of Drug Targeting, 20(6), 524-34. https://doi.org/10.3109/1061186X.2012.693498
Lee Y, et al. Colon-specific Delivery of Celecoxib Is a Potential Strategy to Improve Toxicological and Pharmacological Properties of the Selective Cox-2 Inhibitor: Implication in Treatment of Familiar Adenomatous Polyposis. J Drug Target. 2012;20(6):524-34. PubMed PMID: 22632102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Colon-specific delivery of celecoxib is a potential strategy to improve toxicological and pharmacological properties of the selective Cox-2 inhibitor: implication in treatment of familiar adenomatous polyposis. AU - Lee,Yonghyun, AU - Kim,Hyunjeong, AU - Kim,Wooseong, AU - Yoon,Jeong-Hyun, AU - Jeong,Seong Hoon, AU - Jung,Yunjin, Y1 - 2012/05/27/ PY - 2012/5/29/entrez PY - 2012/5/29/pubmed PY - 2012/10/27/medline SP - 524 EP - 34 JF - Journal of drug targeting JO - J Drug Target VL - 20 IS - 6 N2 - In general, colon-specific delivery of a drug decreases systemic absorption and increases therapeutic concentration of the drug at the target site. N-succinylglutam-1 or 5-yl celecoxib (SG1C and SG5C) were prepared as a colon-specific prodrug of celecoxib, a selective Cox-2 inhibitor, and investigated whether the celecoxib derivatives could deliver celecoxib to the target site and improve cardiovascular toxicity and therapeutic effectiveness for the treatment of familiar adenomatous polyposis. SG1C and SA5C were cleaved to release celecoxib in the cecal contents while stable in small intestinal contents. The cecal release of celecoxib was much greater for SG1C than SG5C. SG1C administered orally was barely detected in the blood and urine. SG1C delivered much greater amount of celecoxib to the large intestine while keeping the plasma concentration of celecoxib at much lower level compared with oral administration of free celecoxib. Consistent with these pharmacokinetic results, SG1C supplied a greater concentration of celecoxib for the entire colonic tissue and did not change the serum level of 6-keto-PGF(1α) whose decrease is associated with the cardiovascular toxicity of celecoxib. Taken together, colon-specific delivery of celecoxib using a prodrug approach may be a useful strategy to improve toxicological and pharmacological properties of celecoxib. SN - 1029-2330 UR - https://www.unboundmedicine.com/medline/citation/22632102/Colon_specific_delivery_of_celecoxib_is_a_potential_strategy_to_improve_toxicological_and_pharmacological_properties_of_the_selective_Cox_2_inhibitor:_implication_in_treatment_of_familiar_adenomatous_polyposis_ L2 - https://www.tandfonline.com/doi/full/10.3109/1061186X.2012.693498 DB - PRIME DP - Unbound Medicine ER -