Gemfibrozil

Molecular formula C15H22O3 Molecular weight 250.3 CAS Registry No. 25812-30-0 

Sample preparation Adjust pH of plasma to 4-5 with phosphoric acid (about 30 jlL phosphoric acid per 4 mL of plasma). 500 p,L Acidified plasma -I- 100 xL 2 pg/mL flurbiprofen in MeCN water 30 70 - 1.3 mL MeCN, vortex, centrifuge at 1000 g for 15 min. Remove the supernatant and add it to 800 pL 1 M pH 3.0 glycine buffer and 4 mL ethyl acetate, shake horizontally at 70 rpm for 15 min, centrifuge at 1000 g for 15 min. Remove the organic layer and evaporate it to dryness in an evacuated centrifuge, reconstitute the residue in 250 xL mobile phase, inject a 10-100 gL aliquot. 

Mobile phase MeCN 10 mM tetrabutylammonium sulfate 28 72, final apparent pH adjusted to 3.5 

Sallustio, B.C. Fairchild, B.A. Biosynthesis, characterization and direct high-performance liquid chromatographic analysis of gemfibrozil 1-0-p-acylglucuronide. J.Chromatogr.B, 1995, 665, 345-353 

Sample preparation 0.5 mL Plasma -t- 0.5 mL 10 p,g/mL IS in MeCN pH 7.4 phosphate buffered saline 1 99 + 20 p.L formic acid + 5 mL cyclohexane ethyl acetate 8 2, extract. Remove the organic layer and evaporate it, reconstitute the residue with 500 p,L mobile phase, inject a 10 pL aliquot. 

The obtained compound 2.46 g were dissolved in 72 ml of diethyl ether and stirred at 3°C. 

To which a solution of manganese sulfate (15 g), 3.1 g of chromium trioxide, 72 ml of water and 3.5 ml of sulfuric acid was added. After stirring for 3.5 hours at 3°C, extracted with diethyl ether. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate-benzene (1 1) as eluent to give 2.35 g of the title compound. 

Therapeutic Function Hypocholesterolemic agent Chemical Name 2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid Common Name — 

With stirring, 44.1 g of isobutyric acid is added to a mixture of 51.0 g of diisopropylamine, 23.2 g of a 57% sodium hydride dispersion in mineral oil, and 350 ml of tetrahydrofuran. When gas evolution subsides, the mixture is heated at reflux for 15 minutes, cooled to 0°C, and treated with 345 ml of a 1.45M solution of n-butyllithium in heptane. After 5 hr, the 

Sample preparation AcUust pH of plasma to 4-5 with phosphoric acid (about 30 (xL phosphoric acid per 4 mL of plasma). 500 p,L Acidified plasma -I- 100 p,L 2 (xg/mL flurbiprofen in MeCN water 30 70 1.3 mL MeCiN, vortex, centrifuge at 1000 g for 15 min. Remove 

Internal standard 4-(2,5-dimethylpheno )-2,2-dimethylbutanoic acid Limit of detection 100 ng/itiL 

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Fibric Acid Derivatives. Fibtic acid derivatives have been used since the 1960s for control of blood Upid levels. The four most well-known compounds in this class ate fenofibrate, gemfibrozil, clofibrate, and bezafibrate, shown in Table 5. Fenofibrate has been the most popular fibtic acid derivative in Europe, and has mote tecentiy been investigated extensively in clinical trials in the United States (153). Bezafibrate is stmcturaHy related to clofibrate, and has tecentiy been reviewed by Western European and AustraUan clinical trials (154). 

Clofibrate, shown to be an effective Upid lowering dmg in the eady 1960s, is the ethyl ester of/ -chlotophenoxy isobutyric acid. Gemfibrozil is a stmctural congener of clofibrate. 

Butyl lithium Doxepin HCI Gemfibrozil Thiothixene Zimel idine... 

While the fibric acid derivatives have antihyperlipidemic effects, their use varies depending on the drug. For example, Clofibrate (Atromid-S) and gemfibrozil (Lopid) are used to treat individuals with very high serum triglyceride levels who present a risk of abdominal pain and pancreatitis and who do not experience a response to diet modifications. Clofibrate is not used for the treatment of other types of hyperlipidemia and is not thought to be effective for prevention of coronary heart disease. Fenofibrate (Tricor) is used as adjunctive treatment for the reduction of LDL, total cholesterol, and triglycerides in patients with hyperlipidemia. 

Gemfibrozil Dizziness or blurred vision may occur. Observe caution when driving or performing hazardous tasks. Notify die primary health care provider if epigastric pain, diarrhea, nausea, or vomiting occurs. 

Lipid regulators gemfibrozil and bezafibrate frequently detected in wastewaters are reported to be eliminated in WWTPs with 46-69% [51] and 36-54% [13]. On the other side, clofibric acid was reported to be refractory pollutant for municipal WWTPs [22]. 

The results showed that the compounds studied with more frequency in the aquatic environment, and of which, logically, there is more information, are the antibiotics, analgesics and anti-inflammatories (like diclofenac, ibuprofen, naproxen, acetylsalicylic acid, and paracetamol), as well as the p-blocker atenolol. In the category of antibiotics, several families are included, like the macrolides (erythromycin), the fluoroquinolones (ofloxacin and ciprofloxacin), sulfonamides (sulfamethoxazole), penicillins (amoxicillin), the metronidazol, and trimethoprim. Other therapeutic groups also widely studied and frequently found in the environmental waters are the lipid regulators (gemfibrozil and bezafibrat), antiepileptic carbamaze-pine, and antidepressants (diazepam, fluoxetine, paroxetine) (see Table 3). 

Because the costs for chronic preventative pharmacotherapy are the same for primary and secondary prevention, while the risk of events is higher with secondary prevention, secondary prevention is more cost effective than primary prevention of CHD. Pharmacotherapy demonstrating cost effectiveness to prevent death in the ACS and post-MI patient includes fibrinolytics ( 2,000 to 33,000 cost per year of life saved), aspirin, glycoprotein Ilb/IIIa receptor blockers ( 13,700 to 16,500 per year of life added), (3-blockers (less than 5,000 to 15,000 cost per year of life saved), ACE inhibitors ( 3,000 to 5,000 cost per year of life saved), eplerenone ( 15,300 to 32,400 per year of life gained), statins ( 4,500 to 9,500 per year of life saved) and gemfibrozil ( 17,000 per year of life saved).49-58 Because cost-effectiveness ratios of less than 50,000 per added life-year are considered economically attractive from a societal perspective,49 pharmacotherapy described above for ACS and secondary prevention are standards of care because of their efficacy and cost attractiveness to payors. 

A fibrate derivative or niacin should be considered in select patients with a low high-density lipoprotein (HDL) cholesterol less than 40 mg/dL (1.04 mmol/L) and/or a high triglyceride level greater than 200 mg/dL (2.26 mmol/L). In a large randomized trial in men with established CAD and low levels of HDL cholesterol, the use of gemfibrozil (600 mg twice daily) significantly decreased the risk of non-fatal myocardial infarction or death from coronary causes.78... 

Chloral hydrate Chloramphenicol Cimetidine Ciprofloxacin Clofibrate Danazol Disulfiram Doxycycline Erythromycin Fenofibrate Fluconazole Fluorouracil Fluoxetine Fluvoxamine Gemfibrozil Influenza vaccine Isoniazid Itraconazole Fovastatin Metronidazole Miconazole Moxalactam Neomycin Norfloxacin Ofloxacin Omeprazole Phenylbutazone Piroxicam Propafenone Propoyxphene Quinidine Sertraline Sulfamethoxazole Sulfinpyrazone Tamoxifen Testosterone Vitamin E Zafirlukast... 

Gemfibrozil 600 mg tablets 1200 mg/day in two doses, 30 minutes before meals abdominal pain, and rash. Increased risk of rhabdomyolysis when given with a statin. Fibric acids are associated with gallstones, myositis, and hepatitis. 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

Centrally acting agents (clonidine, methyldopa, and reserpine) Spironolactone a-Blockers Lipid medications Gemfibrozil Antidepressants... 

Hyperlipidemia Diet HMG-CoA reductase inhibitors (stati ns) Gemfibrozil Ezetemibe CSA greater than TAC consider switch to TAC discontinue or hold SRL CSA/TAC may increase statin levels start at lowest dose Monitor for muscle cramps, CPK levels and LFTs Adjust dose in those with Rl Caution with concomitant statin Often used in combination with a statin... 

TTG may also TLDL and TC greater than ATV regimen, then at least 500 mg/dL => gemfibrozil or... 

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