Rezulin: profile and news

In Latest Drug Scandal, Ketek’s Safety and FDA Approval Are ... May 2, 2006
An analysis of the FDA’s review process (generally) with particular emphasis on what occurred in the case of Rezulin demonstrates the degree to which FDA ... - Newsinferno.com,

Bernstein Research: Euro Pharma- SAN: Acomplia Positive EU Opinion ... May 2, 2006
7: The Rezulin (diabetes) experience suggests Sanofi’s damages, if they ever materialized, might amount to 0.1% of its market cap. ... - PharmaLive.com (press release),

Following suit: More drugs coming under legal attack Apr 21, 2006
...documents. In the past few years, suits over Serzone, an antidepressant, and Rezulin, a diabetes drug, have largely fizzled. "These ... - International Herald Tribune,

Head of Plaintiffs Superfirm Rules Fractious Tribes Apr 24, 2006
...of Propulsid. Another partner, Charles A. Mathis Jr., chaired the executive committee for the MDL against Rezulin. The firm also ... - New York Law Journal,

Vioxx 'Trial in a Box' Cuts Cost of Filing Suit Apr 16, 2006
Premade trial packages aren't new -- they were drawn up in suits over the drugs Propulsid and Rezulin, both withdrawn over safety issues, though those packages ... - Wall Street Journal (subscription),

Other information

Indication
For the treatment of Type II diabetes mellitus

Pharmacology
Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control.

Mechanism Of Action
Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulindependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Unlike sulfonylureas, troglitazone is not an insulin secretagogue.

Drug Category
Vasodilator Agents; Hypoglycemic Agents; Platelet Aggregation Inhibitors; Fibrinolytic Agents; Antineoplastic Agents; ATC:A10BG01

Brand Names/Synonyms
Romglizone; Rezulin; Troglitazone [USAN:BAN:INN]; Prelay; Noscal; Mesylate

Dosage Forms
Not Available

Absorption
Absorbed rapidly. Food increases the extent of absorption by 30% to 85%.

Interactions
Interactions for Troglitazone: Oral Contraceptives: Administration of Troglitazone with an oral contraceptive containing ethinyl estradiol and norethindrone reduced the plasma concentrations of both by approximately 30% which could result in loss of contraception. Therefore, a higher dose of oral contraceptive or an alternative method of contraception should be considered. Terfenadine: Coadministration of Troglitazone with terfenadine decreases the plasma concentration of both terfenadine and its active metabolite by 50-70% and may result in decreased efficacy of terfenadine. Cholestyramine: Concomitant administration of cholestyramine with Troglitazone reduces the absorption of troglitazone by 70%; thus, coadministration of cholestyramine and Troglitazone is not recommended. Glyburide: Coadministration of Troglitazone and glyburide does not appear to alter troglitazone or glyburide pharmacokinetics. Digoxin: Coadministratjon of Troglitazone with digoxin does not alter the steady-state pharmacokinetics of digoxin. Warfarin: Troglitazone has no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin therapy. Acetaminophen: Coadministration of acetaminophen and Troglitazone does not alter the pharmacokinetics of either drug. Metformin: No information is available on the use of Troglitazone with metformin. Ethanol: A single administration of a moderate amount of alcohol did not increase the risk of acute hypoglycemia in Troglitazone-treated patients with type II diabetes mellitus. The above interactions with terfenadine and oral contraceptives suggest that troglitazone may induce drug metabolism by CYP3A4. Studies have not been performed with other drugs metabolized by this enzyme such as: astemizole, calcium channel blockers, cisapride, corticosteroids cyclosporine. HMG-CoA reductase inhibitors, tacrolimus, triazolam, and trimetrexate. The possi bility of altered safety and efficacy should be considered when Troglitazone is used concomitantly with these drugs. Patients stable on one or more of these agents when Troglitazone is started should be closely monitored and their therapy adjusted as necessary.

Chemical IUPAC Name
5-[[4-[(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)methoxy]phenyl]methyl]thiazolidine-2,4-dione

Chemical Formula
C24H27NO5S

Half Life
16-34 hours

Drug Type
Approved Drug

# Accession No
APRD00488

CAS Registry Number
97322-87-7