Gliclazide

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Gliclazide
Gliclazide.svg
Gliclazide-xtal-1999-ball-and-stick.png
Clinical data
Trade names Diamicron, Diaprel, Azukon, others [1]
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category
  • AU:C
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 10.4 hours
Identifiers
  • N-(hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamoyl)-4-methylbenzenesulfonamide
CAS Number
PubChem CID
DrugBank
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KEGG
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ECHA InfoCard 100.040.221 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H21N3O3S
Molar mass 323.41 g·mol−1
3D model (JSmol)
Melting point 180 to 182 °C (356 to 360 °F)
  • O=S(=O)(c1ccc(cc1)C)NC(=O)NN3CC2CCCC2C3
  • InChI=1S/C15H21N3O3S/c1-11-5-7-14(8-6-11)22(20,21)17-15(19)16-18-9-12-3-2-4-13(12)10-18/h5-8,12-13H,2-4,9-10H2,1H3,(H2,16,17,19) Yes check.svgY
  • Key:BOVGTQGAOIONJV-UHFFFAOYSA-N Yes check.svgY
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Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat type 2 diabetes. [7] It is used when dietary changes, exercise, and weight loss are not enough. [4] It is taken by mouth. [7]

Contents

Side effect may include low blood sugar, vomiting, abdominal pain, rash, and liver problems. [4] [7] Use by those with significant kidney problems or liver problems or who are pregnant is not recommended. [7] [4] Gliclazide is in the sulfonylurea family of medications. [7] It works mostly by increasing the release of insulin. [7]

Gliclazide was patented in 1966 and approved for medical use in 1972. [8] It is on the World Health Organization's List of Essential Medicines. [9] It is not available for sale in the United States. [10]

Medical uses

Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes mellitus of stable, mild, non-ketosis prone, type 2 diabetes. It is used when diabetes cannot be controlled by proper dietary management and exercise and when metformin has already been tried. [11]

National Kidney Foundation (2012 Update) claims that Gliclazide does not require dosage up titration even in end stage kidney disease.

Contraindications

Adverse effects

Common adverse effects over 10%: [13]

Uncommon adverse effect between 1 - 10%: [13]

Rare adverse effects (under 1%): [13]

Interactions

Hyperglycemic action may be caused by danazol, chlorpromazine, glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic action may be potentiated by phenylbutazone, alcohol, fluconazole, β-blockers, and possibly ACE inhibitors. It has been found that rifampin increases gliclazide metabolism in humans in vivo. [15]

Overdose

Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and Monitoring. [16]

Mechanism of action

Gliclazide selectively binds to sulfonylurea receptors (SUR-1) on the surface of the pancreatic beta-cells. It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors (SUR-2A) in the heart. [17] This binding effectively closes these K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocytosis of insulin vesicles leading to insulin release. [18]

The mouse model of Maturity-onset diabetes of the young (MODY) diabetes suggested that the reduced gliclazide clearance stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently and that there was no consistent decrease in gliclazide clearance in randomly selected HNF1A-MODY and HNF4A-MODY patients. [19]

Its classification has been ambiguous, as literature uses it as both a first-generation [20] and second-generation [21] sulfonylurea.

Properties

According to the Biopharmaceutical Classification System (BCS), gliclazide falls under the BCS Class II drug, which is poorly soluble and highly permeable.

Water solubility = 0.027mg/L[ citation needed ]

Metabolism

Gliclazide undergoes extensive metabolism to several inactive metabolites in human beings, mainly methylhydroxygliclazide and carboxygliclazide. CYP2C9 is involved in the formation of hydroxygliclazide in human liver microsomes and in a panel of recombinant human P450s in vitro. [23] [24] But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism. [25] [26]

Related Research Articles

<span class="mw-page-title-main">Hypoglycemia</span> Health condition

Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.

<span class="mw-page-title-main">Glimepiride</span> Medication

Glimepiride is an antidiabetic medication within the sulfonylurea class, primarily prescribed for the management of type 2 diabetes. It is regarded as a second-line option compared to metformin, due to metformin's well-established safety and efficacy. Use of glimepiride is recommended in conjunction with lifestyle modifications such as diet and exercise. It is taken by mouth, reaching a peak effect within three hours and lasting for about a day.

<span class="mw-page-title-main">Metformin</span> Medication used to treat diabetes by reducing glucose levels

Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. Metformin is not associated with weight gain and is taken by mouth.

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Sulfonylurea</span> Class of organic compounds used in medicine and agriculture

Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, a dehydrogenated derivative of urea). The side chains R1 and R2 distinguish various sulfonylureas. Sulfonylureas are the most widely used herbicide.

ATC code A10Drugs used in diabetes is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup A10 is part of the anatomical group A Alimentary tract and metabolism.

Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. Along with neonatal diabetes, MODY is a form of the conditions known as monogenic diabetes. While the more common types of diabetes involve more complex combinations of causes involving multiple genes and environmental factors, each forms of MODY are caused by changes to a single gene (monogenic). GCK-MODY and HNF1A-MODY are the most common forms.

<span class="mw-page-title-main">Tolbutamide</span> Chemical compound

Tolbutamide is a first-generation potassium channel blocker, sulfonylurea oral hypoglycemic medication. This drug may be used in the management of type 2 diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

<span class="mw-page-title-main">Sitagliptin</span> Diabetes medication

Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin.

<span class="mw-page-title-main">Gliquidone</span> Chemical compound

Gliquidone is an anti-diabetic medication in the sulfonylurea class. It is classified as a second-generation sulfonylurea. It is used in the treatment of diabetes mellitus type 2. It is marketed by the pharmaceutical company Boehringer Ingelheim (Germany).

<span class="mw-page-title-main">HNF1A</span> Protein-coding gene in the species Homo sapiens

HNF1 homeobox A, also known as HNF1A, is a human gene on chromosome 12. It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes. Mutations in the HNF1A gene have been known to cause diabetes. The HNF1A gene also contains a SNP associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">ABCC8</span> Protein-coding gene in the species Homo sapiens

ATP-binding cassette transporter sub-family C member 8 is a protein that in humans is encoded by the ABCC8 gene. ABCC8 orthologs have been identified in all mammals for which complete genome data are available.

<span class="mw-page-title-main">Insulin (medication)</span> Use of insulin protein and analogs as medical treatment

As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. Insulin is also used along with glucose to treat hyperkalemia. Typically it is given by injection under the skin, but some forms may also be used by injection into a vein or muscle. There are various types of insulin, suitable for various time spans. The types are often all called insulin in the broad sense, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. It is on the World Health Organization's List of Essential Medicines. In 2021, it was the 179th most commonly prescribed medication in the United States, with more than two million prescriptions.

<span class="mw-page-title-main">MODY 1</span> Medical condition

MODY 1 or HNF4A-MODY is a form of maturity onset diabetes of the young.

MODY 3 or HNF1A-MODY is a form of maturity-onset diabetes of the young. It is caused by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is the most common type of MODY in populations with European ancestry, accounting for about 70% of all cases in Europe. HNF1α is a transcription factor that is thought to control a regulatory network important for differentiation of beta cells. Mutations of this gene lead to reduced beta cell mass or impaired function. MODY 1 and MODY 3 diabetes are clinically similar. About 70% of people develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often be treated with sulfonylureas with excellent results for decades. However, the loss of insulin secretory capacity is slowly progressive and most eventually need insulin.

<span class="mw-page-title-main">Gemigliptin</span> Chemical compound

Gemigliptin (rINN), sold under the brand name Zemiglo, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 inhibitor class of drugs. Glucose lowering effects of DPP-4 inhibitors are mainly mediated by GLP-1 and gastric inhibitory polypeptide (GIP) incretin hormones which are inactivated by DPP-4.

<span class="mw-page-title-main">Glybuzole</span> Chemical compound

Glybuzole is a hypoglycaemic medicine, mainly used to treat diabetes mellitus type 2. It is an oral antidiabetic drug (OAD), when administered in the right dose it will help bring the blood glycose level down by stimulating the insulin production. Similar medicines are glimepiride, glipizide, glibenclamide, gliclazide, and gliquidone.

References

  1. ↑ "Gliclazide - Drugs.com". www.drugs.com. Archived from the original on 27 December 2016. Retrieved 27 December 2016.
  2. ↑ "Gliclazide GH MR, Gliclazide LAPL MR, Gliclazide Lupin MR (Lupin Australia Pty Limited)". Therapeutic Goods Administration (TGA). 5 December 2022. Archived from the original on 18 March 2023. Retrieved 7 April 2023.
  3. ↑ "Product monograph brand safety updates". Health Canada . 7 July 2016. Archived from the original on 29 March 2024. Retrieved 3 April 2024.
  4. 1 2 3 4 "Gliclazide Accord-UK 30mg Prolonged-release Tablets - Summary of Product Characteristics (SmPC)". (emc). 12 February 2021. Archived from the original on 22 September 2022. Retrieved 30 December 2021.
  5. ↑ "Diamicron 30 mg MR Tablets - Summary of Product Characteristics (SmPC)". (emc). 11 May 2020. Archived from the original on 23 December 2023. Retrieved 29 December 2021.
  6. ↑ "Dacadis MR 30mg Modified Release Tablets - Summary of Product Characteristics (SmPC)". (emc). 15 July 2020. Archived from the original on 8 November 2023. Retrieved 29 December 2021.
  7. 1 2 3 4 5 6 British National Formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 474. ISBN   9780857111562.
  8. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 449. ISBN   9783527607495. Archived from the original on 27 December 2016.
  9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. ↑ "Gliclazide Advanced Patient Information - Drugs.com". www.drugs.com. Archived from the original on 27 December 2016. Retrieved 27 December 2016.
  11. ↑ "My Site - Special Article: Remission of Type 2 Diabetes". guidelines.diabetes.ca. Archived from the original on 2 June 2023. Retrieved 1 June 2023.
  12. 1 2 3 4 "GLICLAZIDE 60 MG MR TABLETS DRUG LEAFLET". Drugs.com. Archived from the original on 21 April 2019. Retrieved 23 March 2020.
  13. 1 2 3 4 "Gliclazide". Lexicomp. Wolters Kluwer N.V. Archived from the original on 2 June 2023. Retrieved 1 June 2023.
  14. ↑ Schernthaner G, Grimaldi A, Di Mario U, Drzewoski J, Kempler P, Kvapil M, et al. (August 2004). "GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients". European Journal of Clinical Investigation. 34 (8): 535–542. doi:10.1111/j.1365-2362.2004.01381.x. hdl: 1874/10657 . PMID   15305887. S2CID   13636359.
  15. ↑ Park JY, Kim KA, Park PW, Park CW, Shin JG (October 2003). "Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide". Clinical Pharmacology and Therapeutics. 74 (4): 334–340. doi: 10.1016/S0009-9236(03)00221-2 . PMID   14534520. S2CID   21519151.
  16. ↑ Mégarbane B, Chevillard L, Khoudour N, Declèves X (April 2022). "Gliclazide disposition in overdose - a case report with pharmacokinetic modeling". Clinical Toxicology. 60 (4): 541–542. doi:10.1080/15563650.2021.1993245. PMID   34698608. S2CID   239887850.
  17. ↑ Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM (August 2001). "Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells". Diabetologia. 44 (8): 1019–1025. doi: 10.1007/s001250100595 . PMID   11484080.
  18. ↑ Mégarbane B, Chevillard L, Khoudour N, Declèves X (April 2022). "Gliclazide disposition in overdose - a case report with pharmacokinetic modeling". Clinical Toxicology. 60 (4): 541–542. doi:10.1080/15563650.2021.1993245. PMID   34698608. S2CID   239887850.
  19. ↑ Urbanova J, Andel M, Potockova J, Klima J, Macek J, Ptacek P, et al. (2015). "Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model". Current Pharmaceutical Design. 21 (39): 5736–5748. doi:10.2174/1381612821666151008124036. PMID   26446475.
  20. ↑ Ballagi-Pordány G, Köszeghy A, Koltai MZ, Aranyi Z, Pogátsa G (January 1990). "Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds". Diabetes Research and Clinical Practice. 8 (2): 109–114. doi:10.1016/0168-8227(90)90020-T. PMID   2106423.
  21. ↑ Shimoyama T, Yamaguchi S, Takahashi K, Katsuta H, Ito E, Seki H, et al. (June 2006). "Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation". Metabolism. 55 (6): 722–730. doi:10.1016/j.metabol.2006.01.019. PMID   16713429.
  22. ↑ Mégarbane B, Chevillard L, Khoudour N, Declèves X (April 2022). "Gliclazide disposition in overdose - a case report with pharmacokinetic modeling". Clinical Toxicology. 60 (4): 541–542. doi:10.1080/15563650.2021.1993245. PMID   34698608. S2CID   239887850.
  23. ↑ Rieutord A, Stupans I, Shenfield GM, Gross AS (December 1995). "Gliclazide hydroxylation by rat liver microsomes". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 25 (12): 1345–1354. doi:10.3109/00498259509061922. PMID   8719909.
  24. ↑ Elliot DJ, Lewis BC, Gillam EM, Birkett DJ, Gross AS, Miners JO (October 2007). "Identification of the human cytochromes P450 catalysing the rate-limiting pathways of gliclazide elimination". British Journal of Clinical Pharmacology. 64 (4): 450–457. doi:10.1111/j.1365-2125.2007.02943.x. PMC   2048545 . PMID   17517049.
  25. ↑ Zhang Y, Si D, Chen X, Lin N, Guo Y, Zhou H, Zhong D (July 2007). "Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects". British Journal of Clinical Pharmacology. 64 (1): 67–74. doi:10.1111/j.1365-2125.2007.02846.x. PMC   2000619 . PMID   17298483.
  26. ↑ Xu H, Williams KM, Liauw WS, Murray M, Day RO, McLachlan AJ (April 2008). "Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide". British Journal of Pharmacology. 153 (7): 1579–1586. doi:10.1038/sj.bjp.0707685. PMC   2437900 . PMID   18204476.
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