Xidative strain and cardiovascular risk. JAMA. 2008 Mar 19; 299(11):1265?six. [PubMed: 18349088] 80. Barter PJ, Nicholls S, Rye KA, et al. Antiinflammatory properties of HDL. Circ Res. 2004 Oct 15; 95(8):764?two. [PubMed: 15486323] 81. Krukemyer JJ, Talbert RL. Lovastatin: a new cholesterol-lowering agent. Pharmacotherapy. 1987; 7(six):198?10. [PubMed: 3328165] 82. Zhao XQ, Morse JS, Dowdy AA, et al. Security and Tolerability of Simvastatin Plus Niacin in Individuals With Coronary Artery Illness and Low High-Density Lipoprotein Cholesterol (The HDL Atherosclerosis Remedy Study). Am J Cardiol. 2004; 93:307?12. [PubMed: 14759379]NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptClin Pharmacokinet. Author manuscript; offered in PMC 2014 August 01.Mohammadpour and AkhlaghiPageNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptClin Pharmacokinet. Author manuscript; readily available in PMC 2014 August 01.Fig. 1.Chemical structure of CETP inhibitors with corresponding molecular weightMohammadpour and AkhlaghiPageNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptClin Pharmacokinet. Author manuscript; offered in PMC 2014 August 01.Fig. 2.Schematic diagram showing inhibition of many pathways by CETP inhibitors ABCA1: adenosine triphosphate (ATP)-binding cassette transporter A1; ABCG1: ATPbinding cassette transporter G1; apo B: Apolipoprotein B; apoA-I: Apolipoprotein A-I; CE: cholesteryl esters; CETP: Cholesteryl ester transfer protein; FC: Free of charge Cholesterol; HDL: Higher density lipoprotein; HL: Hepatic lipase; LCAT: Lecithin:cholesterol acyltransferase; LDL: Low density lipoprotein; LDL-R: low-density lipoprotein receptors; PL: Phospholipids; SR-B1: scavenger receptor class B member 1; TG: Triglyceride; VLDL: Quite low density lipoproteinTable IPhysicochemical properties of Cholesterol Ester Transfer Protein (CETP) inhibitorsMolecular formula C26H25F9N2O4 C23H35NO2S C30H25F10NO3 C31H36F6N6O2 7.7 87.four 26 eight.eight 38.8 46 7.1 71.five NA 7.0 59.1 39 XLogP Topological Polar Surface Location (Angstrom squared) CETP IC50 (nM)[67]DrugPharmaceutical companyTorcetrapibPfizerDalcetrapibHoffmann La-RocheAnacetrapibMerck Co.Mohammadpour and AkhlaghiEvacetrapibEli Lilly CompanyNA: not availableIC50 concentration of compound causing a 50 inhibition of CETP activityClin Pharmacokinet. Author manuscript; out there in PMC 2014 August 01.Unless otherwise stated, all data have been obtained from Pubchem compound (http://pubchem.ncbi.nlm.nih.gov/)NIH-PA Author ManuscriptPageNIH-PA Author ManuscriptNIH-PA Author ManuscriptTable IISummary of pharmacokinetic and pharmacodynamic properties of Cholesterol Ester Transfer Protein (CETP) inhibitorsTorcetrapib 60 mg/day 600 mg/day 100 mg/day Dalcetrapib Anacetrapib Evacetrapib 130 mg/dayParameterDosePharmacokinetics 33 to 45 in rat and monkey Exposure is higher in fed than fasted state 6 Hepatic metabolism Oxidation (CYP3A4/5) and glucuronidation To M2, then M1 and M4 To dalcetrapib-thiol (active metabolite), then to dalcetrapib-S-Glu and dalcetrapibS-methyl 25.1256355-53-9 web 5 ?three.1255099-26-3 Chemscene 9 as dalcetrapib-thiol NA NA two Major route as oxidative metabolites 9 to 62 fasted 42?three fed Hydrolysis, glucuronidation, oxidation and methylation Hepatic metabolism Hepatic metabolism Oxidation (CYP3A4 big) and glucuronidation To M1, then M2 and M3 three four Exposure is greater ( 65 ) in fed versus fasted state Exposure is 2? fold higher after low fat meal and six? fold larger after higher fat meal NA 38 in ra.PMID:23667820