Class: Fibric Acid Derivatives
VA Class: CV350
Chemical Name: 5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic acid
Molecular Formula: C15H22O3
CAS Number: 25812-30-0
Brands: Lopid
Introduction
Antilipemic agent; fibric acid derivative.2
Uses for Gemfibrozil
Prevention of Cardiovascular Events
Adjunct to dietary therapy to reduce the risk of developing CHD in patients with type IIb hyperlipoproteinemia without clinical evidence of CHD (primary prevention) who have an inadequate response to dietary management, weight loss, exercise, and drugs known to reduce LDL-cholesterol and increase HDL-cholesterol (e.g., bile acid sequestrants, niacin) and who have low HDL-cholesterol concentrations in addition to elevated LDL-cholesterol and triglycerides.1 67 68 104 105 110 127
Because of potential toxicity, including malignancy, gallbladder disease, abdominal pain leading to appendectomy and other abdominal surgeries, and an increased incidence of noncardiovascular and all-cause mortality associated with the chemically and pharmacologically similar drug, clofibrate (no longer commercially available in the US), the potential benefit of gemfibrozil in treating patients with type IIa hyperlipoproteinemia and elevations of LDL-cholesterol only is unlikely to outweigh the risks of such therapy.1
Manufacturer states that gemfibrozil is not indicated for use in the management of patients with low HDL-cholesterol as their only lipid abnormality (isolated low HDL-cholesterol).1
Reduction of recurrent coronary events†, including death from coronary causes, MI, and stroke in men with clinical evidence of CHD who have low HDL-cholesterol and moderately elevated LDL-cholesterol concentrations.137
Dyslipidemias
Adjunct to dietary therapy in the management of severe hypertriglyceridemia in patients at risk of developing pancreatitis (typically those with serum triglyceride concentrations >2000 mg/dL and elevated concentrations of VLDL-cholesterol and fasting chylomicrons) who do not respond adequately to dietary management.1
Also may be used in patients with triglyceride concentrations of 1000–2000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis;1 however, efficacy in patients with type IV hyperlipoproteinemia and triglyceride concentrations >1000 mg/dL who exhibit type V patterns subsequent to dietary or alcoholic indiscretion has not been adequately studied.1
Manufacturer states that gemfibrozil is not indicated for use in patients with type I hyperlipoproteinemia who have elevated triglyceride and chylomicron concentrations but normal VLDL-cholesterol concentrations.1
Effective in a very limited number of patients with type III hyperlipoproteinemia†17 18 37 38 43 45 49 to decrease elevated triglyceride and cholesterol concentrations associated with this disorder.
Gemfibrozil Dosage and Administration
General
Patients should be placed on a standard lipid-lowering diet before initiation of gemfibrozil therapy and should remain on this diet during treatment with the drug.1
Administration
Oral Administration
Administer orally twice daily, 30 minutes before the morning and evening meals.1
Dosage
Adults
Prevention of Cardiovascular Events
Oral
600 mg twice daily.1 16 17 18 21 22 24 25 26 27 30 31 91 104 106
Monitor lipoprotein concentrations periodically.1 Discontinue therapy in patients who fail to achieve an adequate response after 3 months of therapy.1
Dyslipidemias
Oral
600 mg twice daily.1 16 17 18 21 22 24 25 26 27 30 31 91 104 106
Monitor lipoprotein concentrations periodically.1 Discontinue therapy in patients who fail to achieve an adequate response after 3 months of therapy.1
Cautions for Gemfibrozil
Contraindications
Hepatic impairment, including primary biliary cirrhosis; severe renal impairment; or preexisting gallbladder disease.1
Known hypersensitivity to gemfibrozil or any ingredient in the formulation.1
Warnings/Precautions
Warnings
Cholelithiasis
May increase cholesterol excretion in bile,1 34 61 resulting in cholelithiasis.1 26 34 Cholecystitis and cholelithiasis reported.1 Discontinue therapy if gallbladder studies indicate the presence of gallstones.1
Musculoskeletal Effects
Use may be associated with myositis.1 Myalgia, myopathy, myasthenia, painful extremities, arthralgia, synovitis, and rhabdomyolysis reported.1 Myopathy, rhabdomyolysis, and other complications also reported in patients receiving gemfibrozil concomitantly with certain other antilipemic agents.1
Monitor creatine kinase (CK, creatine phosphokinase, CPK) concentrations in patients reporting adverse musculoskeletal effects.1 108 116 Discontinue therapy if myositis is suspected or diagnosed.1
Effect on Morbidity and Mortality
Effect on cardiovascular mortality not established.1 Because gemfibrozil is chemically, pharmacologically, and clinically similar to other fibric acid derivatives, some adverse effects of clofibrate (no longer commercially available in the US) such as increased incidence of cholelithiasis, cholecystitis requiring surgery, postcholecystectomy complications, malignancy, pancreatitis, appendectomy, gallbladder disease, and increased overall mortality may also apply to gemfibrozil,1 and the usual precautions associated with fibrate therapy should be observed.1
Cataracts
Possible subcapsular bilateral and unilateral cataracts.1
Sensitivity Reactions
Hypersensitivity Reactions
Angioedema, laryngeal edema, urticaria, rash, dermatitis, and pruritus reported.1
Major Toxicities
Hematologic Effects
Mild decreases in hemoglobin,1 2 hematocrit,1 2 38 and leukocyte counts1 2 reported; these counts usually normalize during long-term therapy.1 Severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have occurred rarely; eosinophilia also reported.1
Monitor blood cell counts periodically during the first 12 months of therapy.1
General Precautions
Hepatic Effects
Possible elevations in serum concentrations of aminotransferase (transaminase) (i.e., AST, ALT),1 2 24 25 47 LDH,1 2 bilirubin,1 and alkaline phosphatase.1 2 15 25 47 Serum aminotransferase concentrations usually return slowly to pretreatment values following discontinuance of gemfibrozil.1 Cholestatic jaundice reported.1
Perform liver function tests periodically.1 Discontinue therapy if abnormalities persist.1
Carcinogenicity
Carcinogenicity (e.g., hepatic, Leydig cell tumors) demonstrated in animals.1
Specific Populations
Pregnancy
Category C.1
Lactation
Not known if gemfibrozil is distributed into milk.1 102 Discontinue nursing or the drug.1
Pediatric Use
Safety and efficacy not established.1
Renal Impairment
Possible exacerbation of renal insufficiency in patients with baseline Scr >2 mg/dL.1 Consider use of alternative antilipemic therapy against the risks and benefits of a lower dose of gemfibrozil.1
Common Adverse Effects
GI disturbances (e.g., dyspepsia, abdominal pain, diarrhea, nausea, vomiting, constipation, acute appendicitis, gallbladder surgery), adverse CNS effects (headache, hypesthesia, paresthesias, dizziness, somnolence, peripheral neuritis, depression), fatigue, eczema, vertigo, taste perversion, blurred vision, decreased libido, impotence.1
Interactions for Gemfibrozil
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
β-Adrenergic blocking agents | Possible increase in serum triglyceride and decreases in HDL-cholesterol concentrations30 74 | |
Anticoagulants, oral (e.g., warfarin) | Potentiation of anticoagulant effects1 102 124 | Use with caution.1 Reduce anticoagulant dosage to maintain PT at desired level to prevent bleeding complications; monitor PT frequently until stabilized1 |
Estrogens | Potential increase in serum triglyceride concentrations73 | |
HMG-CoA reductase inhibitors (Statins) | Increased risk of adverse musculoskeletal effects (e.g., myopathy, rhabdomyolysis)1 | |
Methyldopa | Possible decrease in HDL- and LDL-cholesterol concentrations74 | |
Repaglinide | Increased repaglinide concentrations and half-life, resulting in enhanced and prolonged blood glucose-lowering effects.138 139 Potential for severe hypoglycemia.138 | Patients currently receiving gemfibrozil should not initiate therapy with repaglinide, and vice versa.138 139 Monitor blood glucose and reduce repaglinide dosage as required if drugs already used concomitantly.138 Patients receiving gemfibrozil concomitantly with repaglinide should not receive itraconazole.138 |
Thiazide diuretics | Possible increase in total cholesterol and triglyceride concentrations.74 |
Gemfibrozil Pharmacokinetics
Absorption
Bioavailability
Rapidly and completely absorbed from the GI tract.1 2 7 76
Peak plasma concentrations occur within 1–2 hours.1 2 7 9 Plasma concentrations do not appear to correlate with therapeutic response.29 102
Food
Rate and extent of absorption increased when administered 30 minutes before meals.1
Distribution
Extent
Highest tissue concentrations observed in the liver and kidneys in animals.2
Gemfibrozil crosses the placenta;2 not known if it is distributed into milk.1 102
Plasma Protein Binding
About 95%.2
Elimination
Metabolism
Appears to be metabolized in the liver to 4 major metabolites produced via 3 metabolic pathways.2 7 102 A phenol derivative (metabolite I)2 7 is pharmacologically active.102
Elimination Route
Excreted in urine (70%) in the form of metabolites and in feces (approximately 6%).1
Half-life
1.3–1.5 hours.1 7 9 10
Stability
Storage
Oral
Tablets
20–25°C.1 Protect from light and humidity.1
Actions and SpectrumActions
Decreases serum concentrations of triglycerides,1 15 16 17 18 19 21 22 23 24 26 27 28 29 30 32 33 37 38 45 48 76 91 104 VLDL-cholesterol,1 15 17 18 19 25 33 37 38 45 48 76 and, to a lesser extent, LDL-cholesterol.1 15 33 37 38 45 76 Increases HDL-cholesterol.1 15 16 19 21 22 24 25 26 31 32 33 36 38 45 88 91 Causes a variable reduction in serum total cholesterol,1 15 16 17 18 19 21 24 25 26 27 28 29 30 31 32 33 37 38 48 68 105 106 because the decrease in serum cholesterol is a net result of a decrease in VLDL-cholesterol,18 19 21 25 26 28 32 33 38 45 an increase in HDL-cholesterol,37 68 and an increase15 21 30 33 37 45 91 or decrease in LDL-cholesterol.21 24 26 32 37 38 45
Generally increases LDL-cholesterol in patients with type IV or V hyperlipoproteinemia and decreases LDL-cholesterol in type IIa or IIb disorder.21 25 28 45 91
Inhibits lipolysis of fat in adipose tissue1 54 56 75 76 91 and decreases hepatic uptake of plasma free fatty acids1 54 75 76 (i.e., free fatty acid turnover is decreased),51 54 75 thereby reducing hepatic triglyceride production1 54 75 76 (triglyceride turnover rate is decreased).51 75 Also inhibits production1 15 54 75 91 and increases clearance1 75 102 of VLDL carrier apolipoprotein B (VLDL-apo B), leading to a decrease in VLDL production,1 15 45 54 75 enhanced clearance of VLDL,15 and, subsequently, a decrease in serum triglyceride concentrations.2 54 91
Advice to Patients
Importance of patients informing clinicians of any unexplained muscle pain, tenderness, or weakness.1
Importance of adhering to nondrug therapies and measures, including dietary management, weight control, physical activity, and management of potentially contributory disease (e.g., diabetes mellitus).1 64 67 70 133 136
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 600 mg* | Gemfibrozil Tablets | Mylan, Sandoz, Teva, Watson |
Lopid (with parabens; scored) | Pfizer |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Gemfibrozil 600MG Tablets (CAMBER PHARMACEUTICALS): 60/$22.99 or 90/$29.98
Lopid 600MG Tablets (PFIZER U.S.): 60/$163.98 or 180/$470.99
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Parke-Davis. Lopid (gemfibrozil) tablets prescribing information. New York, NY; 2003 Oct.
2. Parke-Davis. Lopid (gemfibrozil) compendium of pharmacological and clinical studies. Morris Plains, NJ; 1982 Feb.
3. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985: 457.
4. Hodges RM. Gemfibrozil—a new lipid lowering agent. Proc R Soc Med. 1976; 69(Suppl 2):1-2. [PubMed 798192]
5. Creger PL, Moersch GW, Neuklis WA. Structure/activity relationship of gemfibrozil (CI-719) and related compounds. Proc R Soc Med. 1976; 69(Suppl 2):3-5. [PubMed 1019152]
6. Rodney G, Uhlendorf P, Maxwell RE. The hypolipidaemic effect of gemfibrozil (CI-719) in laboratory animals. Proc R Soc Med. 1976; 69(Suppl 2):6-10. [PubMed 828263]
7. Okerholm RA, Keeley FJ, Peterson FE et al. The metabolism of gemfibrozil. Proc R Soc Med. 1976; 69(Suppl 2):11-4. [PubMed 828261]
8. Kurtz SM, Fitzgerald JE, Fisken RA et al. Toxicological studies on gemfibrozil. Proc R Soc Med. 1976; 69(Suppl 2):15-23. [PubMed 828262]
9. Smith TC. Toleration and bioavailability of gemfibrozil in healthy men. Proc R Soc Med. 1976; 69(Suppl 2):24-7. [PubMed 798193]
10. Randinitis EJ, Kinkel AW, Nelson C et al. Gas chromatographic determination of gemfibrozil and its metabolites in plasma and urine. J Chromatogr. 1984; 307:210-5. [PubMed 6586728]
11. Gray RH, de la Iglesia FA. Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibrozil in several species. Hepatology. 1984; 4:520-30. [PubMed 6586630]
12. de la Iglesia FA, Lewis JE, Buchanan RA et al. Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment. Atherosclerosis. 1982; 43:19-37. [PubMed 6807326]
13. Maxwell RE, Nawrocki JW, Uhlendorf PD. Some comparative effects of gemfibrozil, clofibrate, benzafibrate, cholestyramine, and compactin on sterol metabolism in rats. Atherosclerosis. 1983; 48:195-203. [PubMed 6579963]
14. Kahonen MT, Ylikahri RH. Effect of clofibrate and gemfibrozil on the activities of mitochondrial carnitine acyltransferases in rat liver. Dose-response relations. Atherosclerosis. 1979; 32:47-56. [PubMed 465113]
15. Kesaniemi YA, Grundy SM. Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man. JAMA. 1984; 251:2241-6. [IDIS 184352] [PubMed 6368883]
16. Kaukola S, Manninen V, Malkonen M et al. Gemfibrozil in the treatment of dyslipidaemias in middle-aged survivors of myocardial infarction. Acta Med Scand. 1981; 209:69-73. [IDIS 130843] [PubMed 7010929]
17. Konttinen A, Kuisma I, Ralli R et al. The effect of gemfibrozil on serum lipids in diabetic patients. Ann Clin Res. 1979; 11:240-5. [PubMed 398183]
18. Hoogwerf BJ, Bantle JP, Kuba K et al. Treatment of type III hyperlipoproteinemia with four different treatment regimens. Atherosclerosis. 1984; 51:251-9. [PubMed 6588975]
19. Nye ER, Sutherland NHF, Temples WA. The treatment of hyperlipoproteinemia with gemfibrozil compared with placebo and clofibrate. N Z Med J. 1980; 92:345-9. [IDIS 127495] [PubMed 6935550]
20. Nash DT. Gemfibrozil in combination with other drugs for severe hyperlipidemia: preliminary study comprising four cases. Postgrad Med. 1983; 73:75-82. [IDIS 168636] [PubMed 6572892]
21. Pickering JE. Clinical results with gemfibrozil. Am J Cardiol. 1983; 52:39-40B.
22. Torstila I, Kaukola S, Manninen V et al. Plasma prekallikrein, kallikrein inhibitors, kininogen and lipids during gemfibrozil treatment in type II dyslipidaemia. Acta Med Scand Suppl. 1982; 668:123-9. [IDIS 168767] [PubMed 6188330]
23. Manninen V. Clinical results with gemfibrozil and background to the Helsinki Heart Study. Am J Cardiol. 1983; 52:35-8B.
24. Manninen V, Malkonen M, Eisalo A et al. Gemfibrozil in the treatment of dyslipidaemia: a 5-year follow-up study. Acta Med Scand (Suppl). 1982: 668:82-7. (IDIS 168759)
25. Samuel P. Effects of gemfibrozil on serum lipids. Am J Med. 1983; 74(Suppl 5A):23-7. [IDIS 171223] [PubMed 6573843]
26. Fenderson RW, Deutsch S, Menachemi E et al. Effect of gemfibrozil on serum lipids in man. Angiology. 1982; 33:581-93. [PubMed 6751166]
27. Nash DT. Hyperlipoproteinemia, atherosclerosis and gemfibrozil. Angiology. 1982; 33:594-602. [PubMed 6957155]
28. Lewis JE. Long-term use of gemfibrozil (Lopid) in the treatment of dyslipidemia. Angiology. 1982; 33:603-12. [PubMed 6957156]
29. Jain AK, Ryan JR, LaCorte WSJ et al. Clinical evaluation of gemfibrozil, a new antilipemic agent. Clin Pharmacol Ther. 1981; 29:254-5.
30. Vega GL, Grundy SM. Gemfibrozil therapy in primary hypertriglyceridemia associated with coronary heart disease: effects on metabolism of low-density lipoproteins. JAMA. 1985; 253:2398-403. [IDIS 198753] [PubMed 3856692]
31. Borresen AL, Berg K, Dahlen G et al. The effect of gemfibrozil on human serum apolipoproteins and on serum reserve cholesterol binding capacity (SRCBC). Artery. 1981; 9:77. [PubMed 7018466]
32. Dahlen D, Gillnas T, Borresen AL et al. Effect of gemfibrozil on serum lipid levels. Artery. 1980; 7:224-31. [PubMed 7008748]
33. Schwandt P, Weisweiler P, Neureuther G. Serum lipoprotein lipids after gemfibrozil treatment. Artery. 1979; 5:117-24. [PubMed 231950]
34. Hall MJ, Nelson LM, Russell RI et al. Gemfibrozil—the effect of biliary cholesterol saturation of a new lipid-lowering agent and its comparison with clofibrate. Atherosclerosis. 1981; 39:511-6. [PubMed 6942844]
35. Baird IM, Lewis B, Hill JM. Preliminary observations on the effect of gemfibrozil on the excretion of faecal bile acids. Proc R Soc Med. 1976; 69(Suppl 2):112-4. [PubMed 1019150]
36. Glueck C. Influence of gemfibrozil on high-density lipoproteins. Am J Cardiol. 1983; 52:31-4B.
37. Olsson AG, Rossner S, Walldius G et al. Effect of gemfibrozil on lipoprotein concentrations in different types of hyperlipoproteinaemia. Proc R Soc Med. 1976; 69(Suppl 2):28-31. [PubMed 190607]
38. Vessby B, Lithell J, Boberg J et al. Gemfibrozil as a lipid lowering compound in hyperlipoproteinaemia. A placebo-controlled cross-over trial. Proc R Soc Med. 1976; 69(Suppl 2):32-7. [PubMed 798194]
39. Tuomilehto J, Salonen J, Kuusisto P et al. A clofibrate controlled trial of gemfibrozil in the treatment of hyperlipidaemias. Proc R Soc Med. 1976; 69(Suppl 2):38-40.
40. Beaumont JL, Dachet C. Binding of plasma lipoproteins of chlorophenoxyisobutyric, tibric and nicotinic acids and their esters. Proc R Soc Med. 1976; 69(Suppl 2):41-3. [PubMed 1019153]
41. Eisalo A, Manninen V. Gemfibrozil and clofibrate in the treatment of hyperlipidaemias: a comparative trial. Proc R Soc Med. 1976; 69(Suppl 2):47-8. [PubMed 798197]
42. Eisalo A, Manninen V, Malkonen M et al. Hypolipidaemic action of gemfibrozil in adult nephrotics. Proc R Soc Med. 1976; 69(Suppl 2):47-8. [PubMed 798197]
43. Eisalo A, Manninen V. A long-term trial of gemfibrozil in the treatment of hyperlipidaemias. Proc R Soc Med. 1976; 69(Suppl 2):49-52. [PubMed 798198]
44. Huunan-Seppala A, Manninen V, Burton R et al. Extrinsic factors affecting the response to gemfibrozil. Proc R Soc Med. 1976; 69(Suppl 2):53-7. [PubMed 1019154]
45. Nikkila EA, Ylikahri R, Huttunen JK. Gemfibrozil: effect on serum lipids, lipoproteins, post-heparin plasma lipase activities and glucose tolerance in primary hypertriglyceridaemia. Proc R Soc Med. 1976; 69(Suppl 2):58-63. [PubMed 190608]
46. de Salcedo I, Gorringe JAL, Luiz Salva J et al. Gemfibrozil in a group of diabetics. Proc R Soc Med. 1976; 69(Suppl 2):64-70.
47. Lageder H, Irsigler K. Evaluation of increasing doses of gemfibrozil in hyperlipoproteinaemia. Proc R Soc Med. 1976; 69(Suppl 2):71-5. [PubMed 798199]
48. Janus ED, Costa D, Ononogbu IC et al. The evaluation of lipoprotein changes during gemfibrozil treatment. Proc R Soc Med. 1976; 69(Suppl 2):76-7. [PubMed 1019156]
49. Honorato J, Masso RM, Purroy A. The use of gemfibrozil in the treatment of primary hyperlipoproteinaemia. Preliminary report. Proc R Soc Med. 1976; 69(Suppl 2):78-9. [PubMed 798200]
50. de la Iglesia FA, Pinn SM, Lucas J et al. Quantitative stereology of peroxisomes in hepatocytes from hyperlipoproteinemic patients receiving gemfibrozil. Micron. 1981; 12:97-8.
51. Bremner WF, Third JLHC, Clark B et al. CI-719 in hyperlipoproteinaemia: interim data. Proc R Soc Med. 1976; 69(Suppl 2):83-7. [PubMed 798201]
52. Howard AN, Ghosh P. Gemfibrozil treatment: a comparison with clofibrate. Proc R Soc Med. 1976; 69(Suppl 2):88-9. [PubMed 190609]
53. Wilkening J, Schwandt P. Summary of present data from a clinical trial of CI-719. Proc R Soc Med. 1976; 69(Suppl 2):90-3. [PubMed 1019158]
54. Kissebah AH, Adams PA, Wynn V. Lipokinetic studies with gemfibrozil (CI-719). Proc R Soc Med. 1976; 69(Suppl 2):94-7. [PubMed 190610]
55. Elkeles RS, Ashwell M, Priest R et al. The effect of CI-719 on lipolysis in rat adipose tissue. Proc R Soc Med. 1976; 69(Suppl 2):98-100. [PubMed 1019159]
56. C.dtdon LA. Effect of gemfibrozil in vitro on fat-mobilizing lipolysis in human adipose tissue. Proc R Soc Med. 1976; 69(Suppl 2):101-3.
57. Kallai-Sanfacon MA, Cayen MN, Dubuc J et al. Effect of AY-25, 712 and other lipid-lowering agents on liver catalase and liver carnitine acetyltransferase in rats (41658). Proc Soc Exp Biol Med. 1983; 173:367-71. [PubMed 6867010]
58. O’Brien JR, Etherington MD, Shuttleworth RD et al. A pilot study of the effect of gemfibrozil on some haematological parameters. Thrombosis Res. 1982; 26:275-9.
59. Rasi VPO, Torstila I. Effect of gemfibrozil upon platelet function and blood coagulation. preliminary report. Proc R Soc Med. 1976; 69(Suppl 2):109-11. [PubMed 1019149]
60. Wynn V, chairman. Gemfibrozil: a new lipid lowering agent: open forum. Proc R Soc Med. 1976; 69(Suppl 2):115-20.
61. Leiss O, von Bergmann K, Gnasso A et al. Effect of gemfibrozil on biliary lipid metabolism in normolipemic subjects. Metabolism. 1985; 34:74-82. [PubMed 3855325]
62. Fitzgerald JE, Sanyer JL, Schardein JL et al. Carcinogen bioassay and mutagenicity studies with the hypolipidemic agent gemfibrozil. J Natl Cancer Inst. 1981; 67:1105-14. [PubMed 7029098]
63. Nash DT. Gemfibrozil—a new lipid lowering agent. J Med. 1980; 11:107-16. [PubMed 6931871]
64. National Institutes of Health Office of Medical Applications of Research. Consensus conference: treatment of hypertriglyceridemia. JAMA. 1984; 251:1196-1200. [PubMed 6582287]
65. Levy RI. Current status of the cholesterol controversy. Am J Med. 1983; 74(Suppl 5A):1-4. [PubMed 6342382]
66. Kuo PT. Hyperlipoproteinemia and atherosclerosis: dietary intervention. Am J Med. 1983; 74(Suppl 5A):15-8. [PubMed 6846377]
67. Hunninghake DB. Pharmacologic therapy for the hyperlipidemic patient. Am J Med. 1983; 74(Suppl 5A):19-22. [IDIS 171222] [PubMed 6846378]
68. Anon. Gemfibrozil for hyperlipidemia. Med Lett Drugs Ther. 1982; 24:59-60. [PubMed 6953310]
69. Probstfield JL, Gotto AM Jr. Disorders of lipids and lipoproteins. In: Stein JH, ed. Internal medicine. Boston: Little Brown and Company; 1983:1888-93.
70. National Institutes of Health Office of Medical Applications of Research. Consensus Conference: lowering blood cholesterol to prevent heart disease. JAMA. 1985; 253:2080-6. [PubMed 3974099]
71. Gordon T, Castelli WP, Hjortland MC et al. High density lipoprotein as a protective factor against coronary heart disease: the Framingham study. Am J Med. 1977; 62:707-14. [PubMed 193398]
72. Glueck CJ. Relationship of lipid disorders to coronary heart disease. Am J Med. 1983; 74(Suppl 5A):10-4. [PubMed 6846376]
73. American Heart Association Committee to Design a Dietary Treatment of Hyperlipoproteinemia. Recommendations for treatment of hyperlipidemia in adults: a joint statement of the Nutrition Committee and the Council on Arteriosclerosis. Circulation. 1984; 69:1065-90A. [PubMed 6713610]
74. Weinberger MH. Antihypertensive therapy and lipids: evidence, mechanisms, and implications. Arch Intern Med. 1985; 145:1102-5. [IDIS 200606] [PubMed 2860883]
75. Kissebah AH, Alfarsi S, Adams PW et al. Transport kinetics of plasma free fatty acids, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridemia: effects of 2,2-dimethyl,5(2,5-xylyloxy)valic acid therapy. Atherosclerosis. 1976; 24:199-218. [PubMed 182185]
76. Brown MS, Goldstein JL. Drugs used in the treatment of hyperlipoproteinemias. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York: The Macmillan Company; 1985:827-45.
77. National Heart, Lung, and Blood Institute Lipid Metabolism—Atherogenesis Branch. The lipid research clinics coronary primary prevention trial results: part I. Reduction in incidence of coronary heart disease. JAMA. 1984; 251:351-64. [IDIS 180094] [PubMed 6361299]
78. National Heart, Lung, and Blood Institute Lipid Metabolism—Atherogenesis Branch. The lipid research clinics coronary primary prevention trial results: part II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984; 251:365-74. [IDIS 180095] [PubMed 6361300]
79. Hansten PD. Drug interactions. 5th ed. Philadelphia: Lea & Febiger; 1985:76.
80. Manninen V, Malkonen M. Effect of gemfibrozil on the blood levels of the high density lipoprotein subfractions HDL2 and HDL3. Res Clin Forums. 1982; 4:77-83.
81. W.H.O. cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. Report from the Committee of Principal Investigators. Lancet. 1980; 2:379-85.
82. A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate. Report from the Committee of Principal Investigators. Br Heart J. 1978; 40:1069-118. [IDIS 118395] [PubMed 361054]
83. WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Report from the Committee of Principal Investigators. Lancet. 1984; 2:600-4. [IDIS 190015] [PubMed 6147641]
84. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA. 1975; 231:360-81. [IDIS 49334] [PubMed 1088963]
85. The Coronary Drug Project Research Group. Gallbladder disease as a side effect of drugs influencing lipid metabolism: experience in the Coronary Drug Project. N Engl J Med. 1977; 296:1185-90. [IDIS 71278] [PubMed 323705]
86. Oliver MF. Cholesterol, coronaries, clofibrate and death. N Engl J Med. 1978; 299:1360-2. [PubMed 362204]
87. Green KG. Interpretation of clofibrate trial. Lancet. 1984; 2:1095-6. [PubMed 6150164]
88. Glueck CJ. Nonpharmacologic and pharmacologic alteration of high-density lipoprotein cholesterol: therapeutic approaches to prevention of atherosclerosis. Am Heart J. 1985; 110:1107-15. [IDIS 208439] [PubMed 2865887]
89. American Medical Association Council on Scientific Affairs. Dietary and pharmacologic therapy for the lipid risk factors. JAMA. 1983; 250:1873-9. [IDIS 176576] [PubMed 6620484]
90. Anon. Lipid-lowering drugs. Med Lett Drugs Ther. 1985; 27:74-6. [PubMed 3860714]
91. Saku K, Gartside PS, Hynd BA et al. Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest. 1985; 75:1702-12. [IDIS 199851] [PubMed 3923042]
92. Grundy SM. Consensus statement: role of therapy with “statins” in patients with hypertriglyceridemia. Am J Cardiol. 1998; 81:1-6B. [IDIS 403201] [PubMed 9462596]
93. Mahley RW. Atherogenic lipoproteins and coronary artery disease: concepts derived from recent advances in cellular and molecular biology. Circulation. 1985; 72:943-8. [PubMed 4042302]
94. Reviewers’ comments (personal observations); 1985 Dec.
95. Cheung MC, Albers JJ, Wahl PW et al. High density lipoproteins during hypolipidemic therapy: a comparative study of four drugs. Atherosclerosis. 1980; 35:215-28. [PubMed 7362696]
96. Hazzard WR, Wahl PW, Gagne C et al. Plasma and lipoprotein lipid responses to four hypolipid drugs. Lipids. 1984; 19:73-9. [PubMed 6708754]
97. Pierides AM, Alvarez-Ude F, Kerr DN. Clofibrate-induced muscle damage in patients with chronic renal failure. Lancet. 1975; 2:1279-82. [PubMed 54800]
98. Bridgman JF, Rosen SM, Thorp JM. Complications during clofibrate treatment on nephrotic-syndrome hyperlipoproteinaemia. Lancet. 1972; 2:506-9. [PubMed 4115569]
99. Levy RI, Brensike JF, Epstein SE et al. The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984; 69:325-37. [IDIS 180723] [PubMed 6360415]
100. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore: Williams & Wilkins; 1984:I-10.
101. Brensike JF, Levy RI, Kelsey SF et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984; 69:313-24. [IDIS 180722] [PubMed 6360414]
102. Rhodes DF (Parke-Davis, Morris Plains, NJ): Personal communication; 1986 Jan 21.
103. Hoeg JM, Gregg RE, Brewer HB. An approach to the management of hyperlipoproteinemia. JAMA. 1986; 255:512-21. [IDIS 209539] [PubMed 3510334]
104. Frick MH, Elo O, Haapa K et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987; 317:1237-45. [IDIS 235055] [PubMed 3313041]
105. Rifkind BM. Gemfibrozil, lipids, and coronary risk. N Engl
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