ゲムフィブロジル

ゲムフィブロジル · ロピド · 2,2-ジメチル-5-(2,5-キシリルオキシ)吉草酸 · オルガノリピド · 5-(2,5-ジメチルフェノキシ)-2,2-ジメチルペンタン酸 · ジェムフィブロジル · リポジド · ゲンフィブロジル

識別子と物理属性

CAS No.	25812-30-0
分子式	C15H22O3
平均分子量	250.33 g/mol
単同位体質量	250.15689456 g/mol
SMILES	Cc1ccc(C)c(OCCCC(C)(C)C(=O)O)c1
InChIKey	HEMJJKBWTPKOJG-UHFFFAOYSA-N
PubChem CID	3463
ChEMBL	CHEMBL457
ChEBI	CHEBI:5296
EC No.	247-280-2
DTXSID	DTXSID0020652
現地名	ゲムフィブロジル

化学・物理的性質

XLogP	3.8
極性表面積	46.5
水素結合供与体数	1
水素結合受容体数	3
回転可能結合数	6
重原子数	18
形式電荷	0
複雑度	273
医薬品	Pharmaceuticals -> Antilipidemic AgentsPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Used in Switzerland
LogP（分配係数）	3.4
Color/Form	Crystals from hexane
溶解度	2.78e-02 g/L水にほとんど溶けず、ジクロロメタンに溶けやすく、無水エタノールとメタノールに溶けます。>0.5g/L (温度は記載されていません)
Human Drugs	Breast FeedingLactationMilk, HumanAnticholesteremic AgentsHypolipidemic AgentsFibric acidsFDA approved drugs -> Active ingredient
沸点	159 °C at 0.02 mm Hg158-159 C
融点	58-6162 °C61 - 63 °C61-63°C
Physical Description	Solid
Collision Cross Section	165.5 Å² [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]167.81 Å² [M+Na]+
密度	1.1109 (rough estimate)
屈折率	1.5020 (estimate)
貯蔵条件	2-8°C
外観・状態	粉
pKa（酸解離定数）	4.75±0.45(Predicted)
色	ホワイトからオフホワイト
Merck	14,4388
BCS Class	2
主な用途	法医学と毒物学医薬品（低分子化合物）
InChI	1S/C15H22O3/c1-11-6-7-12(2)13(10-11)18-9-5-8-15(3,4)14(16)17/h6-7,10H,5,8-9H2,1-4H3,(H,16,17)
InChIKey	HEMJJKBWTPKOJG-UHFFFAOYSA-N
SMILES	Cc1ccc(C)c(OCCCC(C)(C)C(O)=O)c1
CAS データベース	25812-30-0(CAS DataBase Reference)
EPAの化学物質情報	Pentanoic acid, 5-(2,5-dimethylphenoxy)-2,2-dimethyl- (25812-30-0)

化学的特性

White Crystalline Powder

安全性と法規制

GHS 分類	This chemical does not meet GHS hazard criteria for 0.8% (1 of 133) of reports.WarningH302 (99.2%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P264, P270, P273, P280, P301+P317, P318, P330, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 133 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Danger
規制情報	Hazard Traits - CarcinogenicityReproductive ToxicityStatus: Active Update: 13-03-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/23698Gemfibrozil: Does not have an individual approval but may be used under an appropriate group standard
FDA 要件	The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl gemfibrozil, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Hazard Classes and Categories	Acute Tox. 4 (99.2%)
保管条件	Commercially available gemfibrozil tablets should be stored in tight containers at a temperature less than 30 °C.
処分方法	SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
相互作用	In a randomized crossover study, 24 SLCO181-genotyped healthy volunteers were given daily doses of 1,200 mg gemfibrozil, 40 mg atorvastatin, or placebo, followed by 0.25 mg of repaglinide on day 3. The mean increase in the repaglinide area under the plasma concentration-time curve from 0 hr to infinity (AUC(0-infinity)) produced by gemfibrozil was larger in individuals with the SLCO1B1 c.521CC genotype (n = 6) than in those with the c.521TC (n = 6) and c.521TT (n = 12) genotypes, by factors of 1.56 (P = 0.004) and 1.54 (P = 0.002), respectively. Gemfibrozil prolonged the repaglinide elimination half-life 1.43 times more in the c.521 CC group than in the c.521TT group (P = 0.047), but no differences were seen in the effects on peak plasma concentration (C(max)). While on gemfibrozil, the minimum blood glucose concentration after repaglinide intake was 19% lower in the c.521CC participants than in the c.521TT participants (P = 0.009). In the c.521TT group, atorvastatin intake had the effect of increasing repaglinide Cmax and AUC(0-infinity) by 41% (P = 0.001) and 18% (P = 0.033), respectively. In conclusion, the extent of gemfibrozil-repaglinide interaction depends on SLCO1B1 genotype. Atorvastatin raises plasma repaglinide concentrations, probably by inhibiting organic anion transporting polypeptide 1B1 (OATP1B1).

用途

説明

Gemfibrozil is a peroxisome proliferator-activated receptor α (PPARα) and PPARγ agonist (EC50s = 193.3 and 147.8 μM, respectively, in transactivation assays). In vivo, gemfibrozil (50 mg/kg, p.o.) reduces serum total cholesterol, triglyceride, and LDL levels in a rat model of high-cholesterol diet-induced hyperlipidemia. Gemfibrozil (100 mg/kg per day) reduces atherosclerotic plaque area, superoxide production, and expression of the genes encoding the NF-κB subunit p65 and chemokine (C-C) motif ligand 2 (CCL2) in ApoE-/- mice. Formulations containing gemfibrozil have been used in the treatment of high cholesterol.

使用

Gemfibrozil has been used to to study its effects on cell cycle progression in yeast. It has been used to study the effects of fibrates on cell proliferation and gene expression in human cell lines.

一般的な説明

Gemfibrozil, 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid (Lopid), is a congener of clofibratethat was used first in the treatment of hyperlipoproteinemia inthe mid-1970s. Its mechanism of action and use are similar tothose of clofibrate. Gemfibrozil reduces plasma levels ofVLDL triglycerides and stimulates clearance of VLDL fromplasma. The drug has little effect on cholesterol plasma levelsbut does cause an increase of HDL.Gemfibrozil is absorbed quickly from the gut and excretedunchanged in the urine. The drug has a plasma half-life of1.5 hours, but reduction of plasma VLDL concentration takesbetween 2 and 5 days to become evident. The peak effect of its hypolipidemic action may take up to 4 weeks to becomemanifest.