Troglitazone (Rezulin®, Resulin® or Romozin®) is a member of the drug class of the thiazolidinediones. It was introduced in the late 1990s but turned out to be associated with an idiosyncratic reaction leading to drug-induced hepatitis. It was withdrawn from the USA market on 21 March2000, and from other markets soon afterwards.
Troglitazone, like the other thiazolidinediones (pioglitazone and rosiglitazone), works by activating PPARs (peroxisome proliferator-activated receptors). Troglitazone is a ligand to both PPARα and - more strongly - PPARγ. Troglitazone also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity in addition to its PPAR activation. It has been shown (Aljada et al) to reduce inflammation: troglitazone use was associated with a decrease of nuclear factor kappa-B (NFκB) and a concomitant increase in its inhibitor (IκB). NFκB is an important cellular transcription regulator for the immune response.
References
Aljada A., Garg R., Ghanim H., Mohanty P., Hamouda W., Assian E., Dandona P.: Nuclear factor-κB suppressive and inhibitor-κB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action?J. Clin. Endocrinol. Metab. 2001, 86, 3250-6. Fulltext (http://dx.doi.org/10.1210/jc.86.7.3250). PMID 11443197.
Troglitazone (Rezulin®, Resulin® or Romozin®) is a member of the drug class of the thiazolidinediones.
Troglitazone also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity in addition to its PPAR activation.
It has been shown (Aljada et al) to reduce inflammation: troglitazone use was associated with a decrease of nuclear factor kappa-B (NFκB) and a concomitant increase in its inhibitor (IκB).
The NIDDK announced on June 4th that it would be terminating the troglitazone arm of its study [4], and the manufacturers, Warner-Lambert, issued a press release claiming that Audrey had died of ‘complications unrelated to the study or the diabetes medication’; [5].
The FDA panel that approved troglitazone noted that rat liver concentrations of the drug were 30 times greater than those in plasma and commented: ‘at least in rats we have reason to be concerned about what might happen ultimately in liver, a target tissue’ [12].
Troglitazone had long since been discounted as a doomed drug by investors, who are remarkably responsive to safety concerns, but its continued presence on the market may have helped to maintain share prices until the merger came through.
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