What is Troglitazone

7/31/2019 What is Troglitazone

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CONTENT

ADVERSEDRUG

REACTION

REPORTS OFTROGLITAZON

E

PHARMACOVIGELENCE/POST MARKETING

SURVEILLENCE

INTRODUCTION

MECHANISMOF

ACTION

ADVERSEDRUG

REACTION OF

TROGLITAZONE


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What is Troglitazone ?


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Member of

thiazolidinedionedrug class

Also knownRezulin , Resulinand Romazin.

Introduce in late

1990 as


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Who developed andmanufactured ?


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Developed by aJapanese

company, DaiichiSankyo Co., Ltd.

Manufactured inthe United Statesthrough Parke-Davis after beingapproved by theU.S. Food andDrug

Administration


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What Troglitazone do ?


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In early manufactured as thiazolinedine antidiabeticagent that lower blood glucose by improving targetcell response to insulin.

Mechanism of action is dependent on presence ofinsulin for activity.

Decrease hepatic glucose output and increase insulindependent glucose disposal in skeletal muscle.


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BUT!!!

United Kingdomwithdrew troglitazone from itsmarket in December 1997 after

its adverse effects on the liver.

U.S. purged the drug from itsmarket in 2000.


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Mechanism of Action


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Pharmacodynamic


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Pharmacokinetic


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DISTRIBUTION

vTroglitazone is extensively bound ( >99%) to serum albumin.

v Mean apparent volume of distribution(V/F) of troglitazone followingmultiple-dose administration rangesfrom 10.5 to 26.5 Ukg of bodyweight.


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ABSORPTION

vTroglitazone is rapidly absorbed andgiven by oral administration.

v the time for maximum plasmaconcentration (tmax) occurs within 2to 3 hours.

v Food increases the extent of

absorption by 30% to 85%.


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METABOLISM

v Sulfation and glucuronidation is themajor routes of metabolism oftroglitazone

vThus, the major metabolites found inthe plasma were the sulfateconjugate (Metabolite 1) followed bythe quinone metabolite (Metabolite3)


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EXCRETION

v Majority of the active drug andmetabolites of pioglitazone areexcreted in the bile and eliminated in

the feces. Renal elimination isnegligible.

vThe metabolites of rosiglitazone areprimarily excreted in the urine.


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Pharmacovigilance/Post

marketing surveillence


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Click to edit Master subtitle style

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Troglitazone : Approval toWithdrawal


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Comparison of reported cases (n) of severe hepatitis, livertransplant and death related to troglitazone, rosiglitazoneor pioglitazone therapy in type 2 diabetic patients


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ADVERSE DRUGREACTION OF

TROGLITAZONE


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1.Hepatotoxicityq Hepatic side


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4. Metabolic effects

q Metabolic side effects including small changes in lipid levels

5. Hematologic disorders

q Small decreases in hemoglobin, hematocrit, and neutrophilcounts

q Typically occur in the first four to eight weeks of therapy andmay be related to an increase in plasma volume.

6. Others


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BENEFITS OFTROGLITAZONE

v Type II diabetes mellitus drug

v Anti-inflammatory drug

v Promotes ovulation


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RISK OF TROGLITAZONE

1. Kidney disease

1. Heart failure

1. Thyroid disease

1. Type 1 diabetes mellitus (insulin-dependentdiabetes)

1. have a serious infection, illness, or injury

*may need to lower the dosage*

.

Troglitazone is in the FDA pregnancy category B.


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ADVERSE DRUG

REACTION REPORTS OFTROGLITAZONE


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Troglitazone (Rezulin)

Indication:

-Antidiabetic agent used for Type II diabetes

ADR Problem: Hepatotoxicity Severe liver toxicity (since 1997)

Liver injury and liver failure (90 cases of liver failure)

Case of liver transplantation and deaths reported

Drug interaction

Warfarin : Few reports of this interaction exist

Warfarin has its effect increased by troglitazone


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What is Troglitazone