Barter - Figure 21 - Final adverse effect Text
This Figure lists a further off-target pharmacologic effect of torcetrapib: it induces the synthesis and secretion of both aldosterone and cortisol from human adrenal cortical cells in tissue culture, and importantly, other CETP inhibitors such as dalcetrapib and anacetrapib do not have these off-target effects.[21][22][23]
J Clin Lipidol. 2011; 5(6).References
[21]Forrest MJ, Bloomfield D, Briscoe RJ, Brown PN, Cumiskey AM, Ehrhart J, Hershey JC, Keller WJ, Ma X, McPherson HE, Messina E, Peterson LB, Sharif-Rodriguez W, Siegl PK, Sinclair PJ, Sparrow CP, Stevenson AS, Sun SY, Tsai C, Vargas H, Walker M III, West SH, White V, Woltmann RF. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol. 2008; 154: 1465–1473.
[22]Hu X, Dietz JD, Xia C, et al. Torcetrapib Induces Aldosterone and Cortisol Production by an Intracellular Calcium-Mediated Mechanism Independently of Cholesteryl Ester Transfer Protein Inhibition. Endocrinology 2009:150:2211-2219.
[23]Capponi AM, Clerc RG, Campos L. No increase in the in vitro production of aldosterone or the expression of CYP11B2 with the CETP modulator dalcetrapib (RO4607381/JTT- 705), in contrast with torcetrapib. Circulation. 2008;118(Suppl 2):S452