Not to be confused with glipizide or glyburide.
Gliclazide
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| Systematic (IUPAC) name |
| N-(hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamoyl)-4-methylbenzenesulfonamide |
| Clinical data |
| AHFS/Drugs.com |
Micromedex Detailed Consumer Information |
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Pregnancy
category
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| Legal status |
- AU: Prescription Only (S4)
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| Pharmacokinetic data |
| Half-life |
10.4 hours |
| Identifiers |
| CAS number |
21187-98-4 Y |
| ATC code |
A10BB09 |
| PubChem |
CID 3475 |
| DrugBank |
DB01120 |
| ChemSpider |
3356 Y |
| UNII |
G4PX8C4HKV Y |
| KEGG |
D01599 Y |
| ChEBI |
CHEBI:31654 Y |
| ChEMBL |
CHEMBL427216 Y |
| Chemical data |
| Formula |
C15H21N3O3S |
| Molecular mass |
323.412 g/mol |
SMILES
- O=S(=O)(c1ccc(cc1)C)NC(=O)NN3CC2CCCC2C3
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InChI
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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) Y
Key:BOVGTQGAOIONJV-UHFFFAOYSA-N Y
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| Y (what is this?) (verify) |
Gliclazide is an oral hypoglycemic (anti-diabetic drug) and is classified as a sulfonylurea. Its classification has been ambiguous, as literature uses it as both a first-generation [1] and second-generation[2] sulfonylurea. Gliclazide was shown to protect human pancreatic beta-cells from hyperglycemia-induced apoptosis.[3] It was also shown to have an antiatherogenic effect (preventing accumulation of fat in arteries) in type 2 diabetes.[4]
Contents
- 1 Form and composition
- 2 Indication
- 3 Mechanism of action
- 4 Dosage
- 5 Properties
- 6 Contraindications
- 7 Metabolism
- 8 Interactions
- 9 Adverse effects
- 10 Overdosage
- 11 References
- 12 External links
§Form and composition
Each immediate-release tablet contains 80 mg. Modified release formulations contain 30 mg and 60 mg of gliclazide.
§Indication
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 or when insulin therapy is not appropriate.[citation needed] National Kidney Foundation (2012 Update) claims that Gliclazide does not require dosage uptitration even in end stage Kidney disease.
§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.[5] This binding effectively closes the K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca++ ion channels to open increasing the Ca++ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocytosis of insulin vesicles leading to insulin release.[citation needed]
§Dosage
The dosage for the 80 mg formulation is 40 to 320 mg daily in two divided doses, while the 30 mg and 60 mg modified release formulation may be given at a dose of 30 to 120 mg once daily at breakfast.[citation needed]
§Properties
Water Solubility = 0.027 mg/L[6]
- Hypoglycemic sulfonylurea, restoring first peak of insulin secretion, increasing insulin sensitivity.[citation needed]
- Glycemia-independent hemovascular effects, antioxidant effect.[citation needed]
- No active circulating metabolites.[citation needed]
§Contraindications
- Type 1 diabetes[citation needed]
- Hypersensitivity to sulfonylureas[citation needed]
- Severe renal or hepatic failure[citation needed] (But relatively useful in mild renal impairment e.g. CKD stage 3)
- Pregnancy and lactation[citation needed]
- Miconazole coprescription[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 hydroxygliclazde in human liver microsomes and in a panel of recombinant human P450sin vitro.[7][8] But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.[9][10]
§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.[11]
§Adverse effects
- Hypoglycemia - while it was shown to have the same efficacy as glimepiride, one of the newer sulfonylureas, the European GUIDE study has shown that it has approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.[12]
- Gastrointestinal disturbance (reported)[citation needed]
- Skin reactions (rare)[citation needed]
- Hematological disorders (rare)[citation needed]
- Hepatic enzyme rises (exceptional)[citation needed]
§Overdosage
Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and monitoring.[citation needed]
§References
- ^ Ballagi-Pordány, György; Köszeghy, Anna; Koltai, Mária-Zsófia; Aranyi, Zoltán; Pogátsa, Gábor (1990). "Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds". Diabetes Research and Clinical Practice 8 (2): 109–14. doi:10.1016/0168-8227(90)90020-T. PMID 2106423.
- ^ Shimoyama, Tatsuhiro; Yamaguchi, Shinya; Takahashi, Kazuto; Katsuta, Hidenori; Ito, Eisuke; Seki, Hiroyuki; Ushikawa, Kenji; Katahira, Hiroshi et al. (2006). "Gliclazide protects 3T3L1 adipocytes against insulin resistance induced by hydrogen peroxide with restoration of GLUT4 translocation". Metabolism 55 (6): 722–30. doi:10.1016/j.metabol.2006.01.019. PMID 16713429.
- ^ Del Guerra, S; Grupillo, M; Masini, M; Lupi, R; Bugliani, M; Torri, S; Boggi, U; Del Chiaro, M et al. (2007). "Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose". Diabetes/Metabolism Research and Reviews 23 (3): 234–8. doi:10.1002/dmrr.680. PMID 16952202.
- ^ Katakami, N.; Yamasaki, Y.; Hayaishi-Okano, R.; Ohtoshi, K.; Kaneto, H.; Matsuhisa, M.; Kosugi, K.; Hori, M. (2004). "Metformin or gliclazide, rather than glibenclamide, attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes". Diabetologia 47 (11): 1906–13. doi:10.1007/s00125-004-1547-8. PMID 15565373.
- ^ Lawrence, C. L.; Proks, P.; Rodrigo, G. C.; Jones, P.; Hayabuchi, Y.; Standen, N. B.; Ashcroft, F. M. (2001). "Gliclazide produces high-affinity block of K ATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells". Diabetologia 44 (8): 1019–25. doi:10.1007/s001250100595. PMID 11484080.
- ^ Gopal Venkatesh Shavi et al. Enhanced dissolution and bioavailability of gliclazide using solid dispersion techniques; International Journal of Drug Delivery 2 (2010) 49-57
- ^ Rieutord, A; Stupans, I; Shenfield, GM; Gross, AS (1995). "Gliclazide hydroxylation by rat liver microsomes". Xenobiotica 25 (12): 1345–54. doi:10.3109/00498259509061922. PMID 8719909.
- ^ Elliot, David J.; Lewis, Benjamin C.; Gillam, Elizabeth M. J.; Birkett, Donald J.; Gross, Annette S.; Miners, John O.; Miners, JO (2007). "Identification of the human cytochromes P450 catalysing the rate-limiting pathways of gliclazide elimination". British Journal of Clinical Pharmacology 64 (4): 450–7. doi:10.1111/j.1365-2125.2007.02943.x. PMC 2048545. PMID 17517049.
- ^ Zhang, Yifan; Si, Dayong; Chen, Xiaoyan; Lin, Nan; Guo, Yingjie; Zhou, Hui; Zhong, Dafang (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.
- ^ Xu, H; Williams, K M; Liauw, W S; Murray, M; Day, R O; McLachlan, A J (2009). "Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide". British Journal of Pharmacology 153 (7): 1579–86. doi:10.1038/sj.bjp.0707685. PMC 2437900. PMID 18204476.
- ^ Park, J; Kim, KA; Park, PW; Park, CW; Shin, JG (2003). "Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide". Clinical Pharmacology & Therapeutics 74 (4): 334–40. doi:10.1016/S0009-9236(03)00221-2. PMID 14534520.
- ^ Schernthaner, G.; Grimaldi, A.; Di Mario, U.; Drzewoski, J.; Kempler, P.; Kvapil, M.; Novials, A.; Rottiers, R. et al. (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): 535–42. doi:10.1111/j.1365-2362.2004.01381.x. PMID 15305887.
§External links
- Official website for Diamicron MR
- SERVIER
- Advance clinical trial on diabetes
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Oral anti-diabetic drugs and Insulin analogs (A10)
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| Insulin |
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Sensitizers
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Biguanides
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- Metformin#
- Buformin‡
- Phenformin‡
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TZDs/"glitazones" (PPAR)
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- Pioglitazone
- Rivoglitazone†
- Rosiglitazone
- Troglitazone‡
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Dual PPAR agonists
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- Aleglitazar†
- Muraglitazar§
- Saroglitazar
- Tesaglitazar§
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Secretagogues
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K+ ATP
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Sulfonylureas
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- 1st generation: Acetohexamide
- Carbutamide
- Chlorpropamide
- Metahexamide
- Tolbutamide
- Tolazamide
2nd generation: Glibenclamide (Glyburide)#
- Glibornuride
- Glipizide
- Gliquidone
- Glisoxepide
- Glyclopyramide
- Glimepiride
- Gliclazide
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Meglitinides/"glinides"
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- Nateglinide
- Repaglinide
- Mitiglinide
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GLP-1 agonists
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- Exenatide
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- Semaglutide
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DPP-4 inhibitors
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GPR40 Free fatty acid receptor 1
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Analogs/other insulins
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- fast-acting (Insulin lispro
- Insulin aspart
- Insulin glulisine)
- short-acting (Regular insulin)
- long-acting (Insulin glargine
- Insulin detemir
- NPH insulin)
- ultra-long-acting (Insulin degludec†)
- inhalable Exubera
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| Other |
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Alpha-glucosidase inhibitors
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Amylin analog
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SGLT2 inhibitors
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Other
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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| Description |
- Glands
- Hormones
- Physiology
- Development
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| Disease |
- Diabetes
- Congenital
- Neoplasms and cancer
- Other
- Symptoms and signs
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| Treatment |
- Procedures
- Drugs
- calcium balance
- corticosteroids
- oral hypoglycemics
- pituitary and hypothalamic
- thyroid
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