| pubmed-article:18838506 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C0608437 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C0038878 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C0040209 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C0036576 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C0022702 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C1707455 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C0182400 | lld:lifeskim |
| pubmed-article:18838506 | lifeskim:mentions | umls-concept:C1710236 | lld:lifeskim |
| pubmed-article:18838506 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:18838506 | pubmed:dateCreated | 2008-12-24 | lld:pubmed |
| pubmed-article:18838506 | pubmed:abstractText | In vitro experiments were conducted to compare k(inact), K(I) and inactivation efficiency (k(inact)/K(I)) of cytochrome P450 (P450) 2C9 by tienilic acid and (+/-)-suprofen using (S)-flurbiprofen, diclofenac, and (S)-warfarin as reporter substrates. Although the inactivation of P450 2C9 by tienilic acid when (S)-flurbiprofen and diclofenac were used as substrates was similar (efficiency of approximately 9 ml/min/micromol), the inactivation kinetics were characterized by a sigmoidal profile. (+/-)-Suprofen inactivation of (S)-flurbiprofen and diclofenac hydroxylation was also described by a sigmoidal profile, although inactivation was markedly less efficient (approximately 1 ml/min/micromol). In contrast, inactivation of P450 2C9-mediated (S)-warfarin 7-hydroxylation by tienilic acid and (+/-)-suprofen was best fit to a hyperbolic equation, where inactivation efficiency was moderately higher (10 ml/min/micromol) and approximately 3-fold higher (3 ml/min/micromol), respectively, relative to that of the other probe substrates, which argues for careful consideration of reporter substrate when mechanism-based inactivation of P450 2C9 is assessed in vitro. Further investigations into the increased inactivation seen with tienilic acid relative to that with (+/-)-suprofen revealed that tienilic acid is a higher affinity substrate with a spectral binding affinity constant (K(s)) of 2 microM and an in vitro half-life of 5 min compared with a K(s) of 21 microM and a 50 min in vitro half-life for (+/-)-suprofen. Lastly, a close analog of tienilic acid with the carboxylate functionality replaced by an oxirane ring was devoid of inactivation properties, which suggests that an ionic binding interaction with a positively charged residue in the P450 2C9 active site is critical for recognition and mechanism-based inactivation by these close structural analogs. | lld:pubmed |
| pubmed-article:18838506 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18838506 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18838506 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18838506 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:18838506 | pubmed:issn | 1521-009X | lld:pubmed |
| pubmed-article:18838506 | pubmed:author | pubmed-author:HutzlerJ... | lld:pubmed |
| pubmed-article:18838506 | pubmed:author | pubmed-author:TracyTimothy... | lld:pubmed |
| pubmed-article:18838506 | pubmed:author | pubmed-author:KumarVikasV | lld:pubmed |
| pubmed-article:18838506 | pubmed:author | pubmed-author:ZientekMichae... | lld:pubmed |
| pubmed-article:18838506 | pubmed:author | pubmed-author:BaloghLarissa... | lld:pubmed |
| pubmed-article:18838506 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18838506 | pubmed:volume | 37 | lld:pubmed |
| pubmed-article:18838506 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18838506 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18838506 | pubmed:pagination | 59-65 | lld:pubmed |
| pubmed-article:18838506 | pubmed:dateRevised | 2010-9-21 | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:meshHeading | pubmed-meshheading:18838506... | lld:pubmed |
| pubmed-article:18838506 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:18838506 | pubmed:articleTitle | Mechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (+/-)-suprofen: a comparison of kinetics and probe substrate selection. | lld:pubmed |
| pubmed-article:18838506 | pubmed:affiliation | Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, St. Louis Laboratories, St. Louis, Missouri, USA. j.matt.hutzler@pfizer.com | lld:pubmed |
| pubmed-article:18838506 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18838506 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:18838506 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
