Actions of Glustazon in details
Oral hypoglycemic agent.
Pharmacology: Pharmacodynamics: Glustazon, a potent and highly selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is a thiazolidinedione oral antidiabetic agent that acts primarily by reducing insulin resistance. It improves glycemic control by increasing insulin sensitivity in target tissues, primarily skeletal muscle and adipose tissue, and by decreasing hepatic gluconeogenesis.
Activation of PPARγ nuclear receptors, which are found in key target tissues for insulin action (eg, adipose tissue, skeletal muscle, liver), modulates the transcription of insulin-responsive genes involved in the control of glucose and lipid metabolism.
Like other thiazolidinediones, Glustazon minimizes the risk of hypoglycemia associated with the treatment of type 2 diabetes by decreasing insulin resistance without stimulating insulin release from pancreatic β-cells.
Pharmacokinetics: Glustazon is absorbed rapidly with peak plasma concentrations occurring within 2 hrs after oral administration (fasting state). Repeated dosing does not result in accumulation of Glustazon or metabolites. Glustazon is >80% bioavailable. While food slightly delays Glustazon's absorption, the extent of absorption is not altered.
Glustazon is >99% plasma protein-bound and its mean apparent volume of distribution after single-dose administration is about 0.63±0.41 L/kg bodyweight. Metabolites MIII and MIV are also extensively bound to serum albumin (>98%).
Glustazon is extensively metabolized by hydroxylation and oxidation through the cytochrome P-450 isoforms (mainly CYP2C8 and to a lesser degree CYP3A4, with additional contributions from other isoforms including the mainly extrahepatic CYP1A1); the metabolites are also partly converted to glucuronide or sulfate conjugates. M-II, M-III and M-IV are its pharmacologically active metabolites. Studies of Glustazon in combination with P450 inhibitors and substrates have been performed and have shown that Glustazon is not a strong CYP3A4 enzyme inducer.
Steady-state serum concentrations of both Glustazon and total Glustazon (Glustazon plus active metabolites) are achieved within 7 days. At steady state, 2 of the pharmacologically active metabolites of Glustazon, MIII and MIV, reach serum concentrations equal to or greater than Glustazon. At steady state, in both healthy volunteers and in patients with type 2 diabetes, Glustazon comprises approximately 30-50% of the peak total Glustazon concentrations and 20-25% of the total area under the serum concentration-time-curve (AUC).
Peak plasma concentration (Cmax), AUC and trough serum concentrations (Cmin) for both Glustazon and total Glustazon increase proportionally at doses of 15 mg and 30 mg/day. There is a slightly less than proportional increase for Glustazon and total Glustazon at a dose of 60 mg/day.
Glustazon is primarily excreted through the bile as unchanged drug or as metabolites and eliminated in the feces. About 15-30% of an oral Glustazon dose is recovered in the urine (as metabolites and its conjugates); its renal elimination is negligible. Glustazon’s plasma elimination t½ is up to 7 hrs while its active metabolites have a t½ of up to 24 hrs.
Special Populations: Renal Insufficiency: Compared with normal subjects, the serum elimination t½ of Glustazon, M-III and M-IV remains unchanged in patients with moderate [creatinine clearance (CrCl) 30-60 mL/min] to severe (CrCl <30 mL/min) renal impairment.
Hepatic Insufficiency: Compared with normal subjects, patients with hepatic dysfunction (Child-Pugh Grade B/C) have an approximate 45% reduction in Glustazon and total Glustazon mean peak plasma concentrations and no change in the mean AUC values. Do not initiate the drug in patients who exhibit clinical evidence of active liver disease or serum transaminase levels (ALT) exceed 2.5 times the upper limit of normal.
Elderly: Peak serum concentrations of Glustazon and total Glustazon are not significantly different in healthy elderly subjects. However, the AUC values in these patients are slightly higher and the terminal t½ values slightly longer than for younger subjects. These changes are considered to be clinically irrelevant.
How should I take Glustazon?
Take Glustazon only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.
Carefully follow the special diet your doctor gave you. This is the most important part of controlling your diabetes and will help the medicine work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.
Glustazon should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.
The tablets may be taken with or without food.
Dosing
The dose of Glustazon will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Glustazon. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (tablets):
- For type 2 diabetes:
- Adults—At first, 15 or 30 milligrams (mg) once a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 45 mg once a day.
- Children—Use and dose must be determined by your doctor.
- For type 2 diabetes:
Missed Dose
If you miss a dose of Glustazon, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Glustazon administration
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.
Glustazon is usually taken once daily. You may take the medicine with or without food.
Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office. Visit your doctor regularly.
Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating.
Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection.
Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change.
Ask your doctor how to adjust your Glustazon dose if needed. Do not change your medication dose or schedule without your doctor's advice.
Use Glustazon regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.
Glustazon is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.
Store at room temperature away from moisture, heat, and light.
Glustazon pharmacology
After oral administration Accel-Glustazon is found in fasting plasma after 30 minutes. Cmax in plasma is reached after 2 hours. At ingestion there was a slight increase of Cmax to 3-4 hours, but the extent of absorption was not changed.
Protein binding of human serum, mainly to albumin greater than 99%; binding to other serum proteins less pronounced. The metabolites of Glustazon M-III and M-IV also significantly associated with serum albumin is more than 98%.
Glustazon is extensively metabolized in the liver by hydroxylation and oxidation. Metabolites M-II, M-IV (hydroxy derivatives of Glustazon) and M-III (keto derivative of Glustazon) exhibit pharmacological activity in models of type 2 diabetes in animals. Metabolites also partly converted into conjugates glucuronic or sulfuric acids.
The metabolism of Glustazon in the liver occurs with the participation of isoenzymes CYP2C8 and CYP3A4.
T1/2 of unchanged Glustazon is 3-7 hours, total Glustazon (Glustazon and active metabolites) is 16-24 hours. The clearance of Accel-Glustazon is 5-7 L / h.
After oral administration about 15-30% of the dose of Glustazon is found in urine. Kidneys displayed a negligible amount of Glustazon, mainly in the form of metabolites and their conjugates.
It is believed that the ingestion of large doses is excreted in bile as unchanged and as metabolites and excreted in the feces.
The concentrations of Glustazon and active metabolites in serum remained at a high level 24 h after a single daily dose.
References
- NCIt. "Pioglitazone: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Pioglitazone: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
