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Chemical Compound Review

Tenivastatin     (3R,5R)-7-[(1S,2R,6R,8S,8aS)- 8-(2,2...

Synonyms: SureCN110804, CHEMBL1201391, AC1L21SN, L-654969, 121009-77-6, ...
 
 
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High impact information on simvastatin

  • Further studies conducted in human liver microsomes with atorvastatin (AVA) showed that, as with SVA, GFZ was a less potent inhibitor of the CYP3A4-mediated oxidation of this drug than its glucuronidation [1].
  • In dog and human liver microsomes, GFZ exerted a minimal inhibitory effect on CYP3A-mediated SVA oxidation, but did inhibit SVA glucuronidation [1].
  • Among six human UGT isozymes tested, UGT1A1 and 1A3 were capable of catalyzing the glucuronidation of both GFZ and SVA [1].
  • After i.v. administration of [(14)C]SVA to dogs, GFZ treatment significantly reduced (2-3-fold) the plasma clearance of SVA and the biliary excretion of SVA glucuronide (together with its cyclization product SV), but not the excretion of a major oxidative metabolite of SVA, consistent with the in vitro findings in dogs [1].
 

Associations of simvastatin with other chemical compounds

  • Gemfibrozil (GFZ) modestly affected the formation of beta-oxidative products and CYP3A4-mediated oxidative metabolites of simvastatin hydroxy acid (SVA) but markedly inhibited the glucuronidation-mediated lactonization of SVA and the glucuronidation of a beta-oxidation product (IC(50) approximately 50 and 15 microM, respectively) [2].

References

  1. Mechanistic studies on metabolic interactions between gemfibrozil and statins. Prueksaritanont, T., Zhao, J.J., Ma, B., Roadcap, B.A., Tang, C., Qiu, Y., Liu, L., Lin, J.H., Pearson, P.G., Baillie, T.A. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  2. Effects of fibrates on metabolism of statins in human hepatocytes. Prueksaritanont, T., Tang, C., Qiu, Y., Mu, L., Subramanian, R., Lin, J.H. Drug Metab. Dispos. (2002) [Pubmed]
 
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