Lobeglitazone

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Chemical compound

Pharmaceutical compound

Other namesCKD-501

A10BG04 (WHO)

Lobeglitazone
Clinical data

Trade names	Duvie
Other names	CKD-501
Routes of administration	Oral
ATC code	A10BG04 (WHO)
Legal status
Legal status	Rx-only in South Korea
Pharmacokinetic data
Protein binding	>99%^[1]
Metabolism	liver (CYP2C9, 2C19, and 1A2)^[1]
Elimination half-life	7.8–9.8 hours^[2]
Identifiers
IUPAC name 5-[(4-[2-([6-(4-Methoxyphenoxy)pyrimidin-4-yl]-methylamino)ethoxy]phenyl)methyl]-1,3-thiazolidine-2,4-dione
CAS Number	607723-33-1
PubChem CID	9826451
DrugBank	DB09198^Y
ChemSpider	8002194
UNII	MY89F08K5D
KEGG	D11923
Chemical and physical data
Formula	C₂₄H₂₄N₄O₅S
Molar mass	480.54 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CN(CCOC1=CC=C(C=C1)CC2C(=O)NC(=O)S2)C3=CC(=NC=N3)OC4=CC=C(C=C4)OC
InChI InChI=1S/C24H24N4O5S/c1-28(21-14-22(26-15-25-21)33-19-9-7-17(31-2)8-10-19)11-12-32-18-5-3-16(4-6-18)13-20-23(29)27-24(30)34-20/h3-10,14-15,20H,11-13H2,1-2H3,(H,27,29,30)^Y Key:CHHXEZSCHQVSRE-UHFFFAOYSA-N^Y

Lobeglitazone (trade name Duvie, Chong Kun Dang) is an antidiabetic drug in the thiazolidinedione class of drugs. As an agonist for both PPARα and PPARγ, it works as an insulin sensitizer by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin.^[3]

Lobeglitazone is used to assist regulation of blood glucose level of diabetes mellitus type 2 patients. It can be used alone or in combination with metformin.^[4]

Lobeglitazone was approved by the Ministry of Food and Drug Safety (Korea) in 2013, and the postmarketing surveillance is on progress until 2019.^[4]^[5]^{[needs update]}

Pharmacokinetics

The absolute bioavailability of lobeglitazone is about 95% in rat.^[1] In human, the mean steady state clearance (CL_ss/F) was 1.13 L/h across in 1 to 4 mg dose range. In the dose range, the mean half-life was 10.3 h.^[2] Urine excretion was negligible amount in elimination of lobeglitazone in rat and human.^[1]^[2]

The plasma protein binding of the drug is over 99%.^[1]^[6] The average blood-to-plasma concentration ratio was 0.636. The unbound fraction of lobeglitazone in microsomal incubation medium was 0.479.^[6]

Lobeglitazone was primarily distributed to the liver with tissue-to-plasma concentration ratio as 5.59, and less to heart, lung, and fat. The tissue to plasma concentration ratios were ranged from about 0.25 to 4.0 for major tissues, in rat.^[1]

Among six major membrane transporters recommended by the United States Food and Drug Administration, lobeglitazone interacts with OATP1B1, OAT3, and MDR1.^[1] In vitro, lobeglitazone was a substrate of rodent OATP1B2.^[6] Lobeglitazone interacted with CYP1A2, 2C9 and 2C19.^[1]

Distribution to liver of lobeglitazone was inhibited by atorvastatin, in rats.^[6]

References

1 2 3 4 5 6 7 8 Lee JH, Noh CK, Yim CS, Jeong YS, Ahn SH, Lee W, Kim DD, Chung SJ (2015). "Kinetics of the Absorption, Distribution, Metabolism, and Excretion of Lobeglitazone, a Novel Activator of Peroxisome Proliferator-Activated Receptor Gamma in Rats". Journal of Pharmaceutical Sciences. 104 (9): 3049–3059. doi:10.1002/jps.24378. PMID 25648999.
1 2 3 Kim JW, Kim JR, Yi S, Shin KH, Shin HS, Yoon SH, Cho JY, Kim DH, Shin SG, Jang IJ, Yu KS (2011). "Tolerability and pharmacokinetics of lobeglitazone (CKD-501), a peroxisome proliferator-activated receptor-γ agonist: a single- and multiple-dose, double-blind, randomized control study in healthy male Korean subjects". Clinical Therapeutics. 33 (11): 1819–1830. doi:10.1016/j.clinthera.2011.09.023. PMID 22047812.
↑ Lee JH, Woo YA, Hwang IC, Kim CY, Kim DD, Shim CK, Chung SJ (2009). "Quantification of CKD-501, lobeglitazone, in rat plasma using a liquid-chromatography/tandem mass spectrometry method and its applications to pharmacokinetic studies". Journal of Pharmaceutical and Biomedical Analysis. 50 (5): 872–877. doi:10.1016/j.jpba.2009.06.003. PMID 19577404.
1 2 "MFDS permission information of Duvie Tablet 0.5mg". Ministry of Food and Drug Safety. Archived from the original (Release of Information) on 3 March 2016. Retrieved 23 October 2014.
↑ "국내개발 20번째 신약'듀비에정'허가(20th new drug developed in Korea 'Duvie Tablet' was approved)". Chong Kun Dang press release. 4 July 2013. Archived from the original on 23 September 2015. Retrieved 23 October 2014.
1 2 3 4 Yim CS, Jeong YS, Lee SY, Pyeon W, Ryu HM, Lee JH, Lee KR, Maeng HJ, Chung SJ (2017). "Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for an rOATP1B2-Mediated Interaction in Hepatic Transport". Drug Metabolism and Disposition. 45 (3): 246–259. doi:10.1124/dmd.116.074120. PMID 28069721.

Oral diabetes medication, insulins and insulin analogues, and other drugs used in diabetes (A10)

Insulins and insulin analogues

Fast-acting	Insulin aspart Insulin glulisine Insulin lispro
Short-acting	Regular insulin^#
Long-acting	Insulin detemir^# Insulin glargine^# (+lixisenatide) NPH insulin Lente insulin^‡ Ultralente insulin^‡
Ultra-long-acting	Insulin degludec^# (+insulin aspart, +liraglutide) Insulin icodec^† (+semaglutide)
Inhalable	Exubera^‡ Afrezza
Oral	Insulin tregopil^†

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Non-insulins

Insulin sensitizers

Biguanides	Buformin^‡ Metformin^# Phenformin^‡
TZDs ("-glitazones") and PPAR agonists	Ciglitazone^§ Darglitazone^§ Englitazone^§ Lobeglitazone Netoglitazone^§ Pioglitazone Rivoglitazone^† Rosiglitazone Troglitazone^‡
Dual PPAR agonists	Aleglitazar^† Muraglitazar^§ Saroglitazar Tesaglitazar^§
Amylin analogues and DACRAs	Cagrilintide^§ Pramlintide

Secretagogues

K⁺_ATP

Sulfonylureas	1st generation: Acetohexamide Carbutamide Chlorpropamide Glycyclamide Metahexamide Tolazamide Tolbutamide 2nd generation: Glibenclamide (glyburide) Glibornuride Glicaramide Gliclazide^# Glimepiride Glipizide Gliquidone Glisoxepide Glyclopyramide
Meglitinides ("-glinides")	Mitiglinide Nateglinide Repaglinide

GLP-1 receptor agonists

Albiglutide^‡
Danuglipron^†
Dulaglutide
Exenatide
Liraglutide
Lixisenatide
Orforglipron^†
Semaglutide
Taspoglutide^†

GLP1 poly-agonist peptides	Mazdutide (GLP-1/GCGR) Retatrutide^§ (GLP-1/GIP/GCGR) Tirzepatide (GLP-1/GIP)

DPP-4 inhibitors ("-gliptins")

Alogliptin
Anagliptin
Evogliptin
Garvagliptin
Gemigliptin
Gosogliptin
Linagliptin
Melogliptin
Omarigliptin
Retagliptin
Saxagliptin
Sitagliptin
Teneligliptin
Trelagliptin
Vildagliptin

Other

Aldose reductase inhibitors	Epalrestat Fidarestat^§ Ranirestat^† Tolrestat^‡ Zenarestat^§
Alpha-glucosidase inhibitors	Acarbose Miglitol Voglibose
SGLT2 inhibitors ("-gliflozins")	Canagliflozin Dapagliflozin Empagliflozin^# Ertugliflozin Ipragliflozin Luseogliflozin Remogliflozin^§ Sergliflozin^§ Sotagliflozin Tofogliflozin^† Velagliflozin
Other	Benfluorex^‡ Bromocriptine Imeglimin

Combinations

Alogliptin/metformin
Canagliflozin/metformin
Cagrilintide/semaglutide^§
Dapagliflozin/metformin
Dapagliflozin/saxagliptin
Dapagliflozin/saxagliptin/metformin
Empagliflozin/linagliptin
Empagliflozin/metformin
Gemigliptin/rosuvastatin
Glibenclamide (glyburide)/metformin
Glimepiride/rosiglitazone
Linagliptin/metformin
Metformin/acarbose
Metformin/ertugliflozin
Metformin/evogliptin
Metformin/gemigliptin
Metformin/repaglinide
Metformin/sulfonylureas
Metformin/teneligliptin
Phenformin/sulfonylureas
Pioglitazone/alogliptin
Pioglitazone/glimepiride
Pioglitazone/metformin
Pioglitazone/sitagliptin
Rosiglitazone/metformin
Saxagliptin/metformin
Sitagliptin/dapagliflozin
Sitagliptin/ertugliflozin
Sitagliptin/metformin
Sitagliptin/simvastatin
Vildagliptin/metformin

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

v t e PPARTooltip Peroxisome proliferator-activated receptor modulators
PPARαTooltip Peroxisome proliferator-activated receptor alpha	Agonists: 15-HETE 15-HpETE Aleglitazar Aluminium clofibrate Arachidonic acid Bezafibrate Chiglitazar Clofibrate CP-775146 Daidzein DHEA (prasterone) (in rodents) Elafibranor Etomoxir Fenofibrate Genistein Gemfibrozil GW-7647 Lanifibranor Leukotriene B₄ LG-101506 LG-100754 Lobeglitazone Muraglitazar Oleylethanolamide Palmitoylethanolamide Pemafibrate Perfluorononanoic acid Perfluorooctanoic acid Pioglitazone Saroglitazar Sodelglitazar Tesaglitazar Tetradecylthioacetic acid Troglitazone WY-14643 Antagonists: GW-6471 MK-886
PPARδTooltip Peroxisome proliferator-activated receptor delta	Agonists: 15-HETE 15-HpETE Arachidonic acid Bezafibrate Daidzein Elafibranor Fonadelpar Genistein GW-0742 GW-501516 L-165,041 Lanifibranor LG-101506 Seladelpar Sodelglitazar Tetradecylthioacetic acid Antagonists: FH-535 GSK-0660 GSK-3787
PPARγTooltip Peroxisome proliferator-activated receptor gamma	Agonists: 5-Oxo-ETE 5-Oxo-15-hydroxy-ETE 15-Deoxy-Δ^12,14-prostaglandin J₂ 15-HETE 15-HpETE Aleglitazar Arachidonic acid Balaglitazone Berberine Bezafibrate Cannabidiol Cevoglitazar Chiglitazar Ciglitazone Daidzein Darglitazone Edaglitazone Efatutazone Englitazone Etalocib Farglitazar Genistein GW-1929 Ibuprofen Imiglitazar Indeglitazar Lanifibranor LG-100268 LG-100754 LG-101506 Lobeglitazone Muraglitazar (muroglitazar) nTZDpa Naveglitazar Netoglitazone Oxeglitazar Peliglitazar Pemaglitazar Perfluorononanoic acid Pioglitazone Prostaglandin J₂ Ragaglitazar Reglitazar Rivoglitazone Rosiglitazone RS5444 Saroglitazar Sipoglitazar Sodelglitazar Telmisartan Tesaglitazar Troglitazone SPPARMsTooltip Selective PPARγ modulator: BADGE EPI-001 INT-131 MK-0533 S26948 Antagonists: FH-535 GW-9662 SR-202 T-0070907 Unknown: SR-1664
Non-selective	Agonists: Ciprofibrate Clinofibrate Clofibride Englitazone Etofibrate Farglitazar Netoglitazone Ronifibrate Rivoglitazone Simfibrate
See also Receptor/signaling modulators

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Medicine

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