- Raw materials
- Anti-diabetics
- Glitazones
- Troglitazone
Troglitazone API Manufacturers & Suppliers
0 verified results
All Troglitazone data. Full access. Full negotiation power
Commercial-scale Suppliers
Join our notification list by following this page.
Click the button below to find out more
Click the button below to switch over to the contract services area of Pharmaoffer.
Total market transparency
Supplier trade data access
Buyer / supplier flow comparison
Troglitazone | CAS No: 97322-87-7 | GMP-certified suppliers
A medication that improves insulin sensitivity and lowers blood glucose in type II diabetes mellitus, used alone or with other antidiabetic agents as an adjunct to diet and exercise.
Therapeutic categories
Primary indications
- For the treatment of Type II diabetes mellitus
- It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise
Product Snapshot
- Troglitazone is an oral small molecule formulation
- It is primarily indicated for the treatment of Type II diabetes mellitus as monotherapy or in combination with other antidiabetic agents
- The compound has experienced approval, investigational use, and subsequent withdrawal in various regulatory markets
Clinical Overview
Pharmacodynamically, troglitazone improves insulin sensitivity in peripheral tissues such as muscle and adipose, while concurrently suppressing hepatic gluconeogenesis. Its glucose-lowering effect is dependent on the presence of insulin and is mechanistically distinct from other antidiabetic classes including sulfonylureas and biguanides, as it is not an insulin secretagogue.
The mechanism of action involves troglitazone acting as a ligand for peroxisome proliferator-activated receptors (PPARs), specifically PPARγ with higher affinity, and to a lesser extent PPARα. Activation of these nuclear receptors modulates the transcription of insulin-responsive genes integral to glucose and lipid metabolism. Additionally, troglitazone contains an α-tocopherol (vitamin E-like) moiety, which may confer anti-inflammatory effects, evidenced by modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways.
Pharmacokinetic data indicate that troglitazone is metabolized extensively via cytochrome P450 enzymes, interacting with multiple isoforms including CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4. It functions as both a substrate and modulator (inhibitor or inducer) of these enzymes as well as UGT family isoforms. Troglitazone also inhibits hepatic transporters, such as BSEP (ABCB11) and OATP1B1 (SLCO1B1).
Clinically, troglitazone was withdrawn from the market in 2000 due to serious hepatotoxicity risks, including liver failure. The safety profile prompted its replacement by other thiazolidinediones, notably pioglitazone and rosiglitazone, which exhibit improved hepatic tolerance profiles.
From an API sourcing perspective, given its withdrawn status and safety concerns, troglitazone is primarily of interest for research or comparative pharmacology. Quality assurance should focus on stringent impurity profiling and robust documentation of synthetic origin. Suppliers must comply with regulatory guidelines reflecting its discontinued clinical use and potential toxicity.
Identification & chemistry
| Generic name | Troglitazone |
|---|---|
| Molecule type | Small molecule |
| CAS | 97322-87-7 |
| UNII | I66ZZ0ZN0E |
| DrugBank ID | DB00197 |
Pharmacology
| Summary | Troglitazone is a thiazolidinedione antihyperglycemic agent that improves insulin sensitivity by acting as a ligand for nuclear receptors, primarily PPARγ and PPARα, regulating genes involved in glucose and lipid metabolism. Its pharmacodynamic effects include decreased hepatic glucose production and enhanced insulin-dependent glucose uptake in peripheral tissues. Additionally, troglitazone exhibits anti-inflammatory activity through modulation of NF-κB signaling pathways. |
|---|---|
| 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 insulin dependent 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. Troglitazone is a ligand to both PPARα and PPARγ, with a highter affinity for PPARγ. The drug also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). Unlike sulfonylureas, troglitazone is not an insulin secretagogue. |
| Pharmacodynamics | 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. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Peroxisome proliferator-activated receptor gamma | Humans | agonist, regulator |
| Estrogen-related receptor gamma | Humans | inverse agonist |
| Steroid hormone receptor ERR1 | Humans | inverse agonist |
ADME / PK
| Absorption | Absorbed rapidly. Food increases the extent of absorption by 30% to 85%. |
|---|---|
| Half-life | 16-34 hours |
| Protein binding | > 99% (primarily to serum albumin) |
| Metabolism | A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses. |
Formulation & handling
- Troglitazone is a small molecule intended for oral administration with low water solubility impacting formulation design. Its high LogP value indicates significant lipophilicity, necessitating solubilization strategies for bioavailability enhancement. Stability considerations include protection from conditions that may promote degradation, with no peptide or biologic handling requirements.
Regulatory status
| Lifecycle | The active pharmaceutical ingredient is in a mature market phase in the United States following the expiration of key patents between 2013 and 2017, allowing for generic competition and widespread availability. Products containing this API are primarily marketed in the US with established regulatory approval. |
|---|
Supply Chain
| Supply chain summary | Troglitazone has been manufactured by two originator companies, indicating a limited number of original suppliers in its production landscape. Its branded products have a presence primarily in the United States, as reflected by multiple US patents, with no explicit mention of EU or other regions. The patent expirations, occurring between 2013 and 2017, suggest that generic competition is likely established or upcoming in the market. |
|---|
Troglitazone is a type of Glitazones
Glitazones, also known as thiazolidinediones (TZDs), are a subcategory of pharmaceutical active pharmaceutical ingredients (APIs) widely used in the treatment of type 2 diabetes mellitus. These compounds act as insulin sensitizers, enhancing the body's response to insulin, thereby promoting glucose utilization and regulating blood sugar levels.
Glitazones exert their therapeutic effects by activating the peroxisome proliferator-activated receptor gamma (PPAR-γ), a nuclear receptor found predominantly in adipose tissue. PPAR-γ activation leads to improved insulin sensitivity in adipocytes, skeletal muscle cells, and hepatocytes, resulting in decreased hepatic glucose production and increased glucose uptake in peripheral tissues.
The primary glitazone medications available in the market include rosiglitazone and pioglitazone. These drugs are administered orally and are typically prescribed in conjunction with other antidiabetic medications, such as metformin or sulfonylureas, to achieve optimal glycemic control.
Glitazones are characterized by their high specificity for PPAR-γ receptors, which distinguishes them from other antidiabetic drug classes. However, their use may be associated with certain adverse effects, such as weight gain, fluid retention, and an increased risk of heart failure. Therefore, close monitoring and individual patient assessment are essential when prescribing glitazones.
In conclusion, glitazones are a valuable class of pharmaceutical APIs utilized in the management of type 2 diabetes. Their ability to enhance insulin sensitivity through PPAR-γ activation makes them an effective therapeutic option, albeit with potential side effects that require careful consideration in clinical practice.
Troglitazone (Glitazones), classified under Anti-diabetics
Anti-diabetics, belonging to the pharmaceutical API (Active Pharmaceutical Ingredient) category, are a group of compounds designed to manage and treat diabetes mellitus, a chronic metabolic disorder characterized by high blood sugar levels. These medications play a vital role in controlling diabetes and preventing complications associated with the disease.
Anti-diabetics encompass a wide range of drug classes, including biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Each class works through different mechanisms to regulate blood sugar levels and improve insulin sensitivity.
Biguanides, such as metformin, reduce glucose production by the liver and enhance insulin sensitivity in peripheral tissues. Sulfonylureas, like glipizide, stimulate insulin secretion from pancreatic beta cells. Thiazolidinediones, including pioglitazone, improve insulin sensitivity in muscle and adipose tissues. DPP-4 inhibitors, such as sitagliptin, increase insulin release and inhibit glucagon secretion. SGLT2 inhibitors, like dapagliflozin, decrease renal glucose reabsorption, leading to increased urinary glucose excretion. GLP-1 receptor agonists, such as exenatide, enhance insulin secretion, suppress glucagon release, slow gastric emptying, and promote satiety.
These anti-diabetic APIs serve as the foundational ingredients for the formulation of various oral tablets, capsules, and injectable medications used in the treatment of diabetes. By targeting different aspects of glucose regulation, they help patients achieve and maintain optimal blood sugar levels, thus reducing the risk of diabetic complications, such as cardiovascular disease, neuropathy, and nephropathy.
It is crucial for healthcare professionals to prescribe and administer these anti-diabetic medications appropriately, considering factors like the patient's medical history, co-existing conditions, and potential drug interactions. Regular monitoring of blood glucose levels and close medical supervision are necessary to ensure effective diabetes management.
In conclusion, anti-diabetics form a critical category of pharmaceutical APIs used for the treatment of diabetes. These compounds, encompassing various drug classes, work through distinct mechanisms to regulate blood sugar levels and improve insulin sensitivity. By facilitating glucose control, anti-diabetic APIs help mitigate the risk of complications associated with diabetes mellitus, ultimately promoting better health outcomes for patients.
