Biochemistry and Molecular Biology of Mechanisms of Action of Fibrates – An Overview

Fibrates are a class ofmedication that mainly lowers theblood triglyceride levels. Theyreduce the LDL andincrease the levels of HDL C, in the blood.Clofibrate,the first member to bediscovered in 1962, and introduced in USA in 1967, is withdrawnin 2002, due to unexplained hepatomegaly,hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome, macrovascular and microvascular diabetic complications like stroke, myocardial infarction, peripheral vascular diseaseand diabeticretinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density LipoproteinCholesterol Intervention Trial) , FIELD trail. (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,ACCORD -Lipid trial (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and BIP (Bezafibrate Infarction Prevention Study) trial andangiography trials, like LOCAT(LopidCoronary Angiography Trial) and BECLAIT(Bezafibrate Coronary Atherosclerosis Intervention Trial)demonstrated thebeneficial effects of gemfibrozil and fenofibrate.Their mechanism of action remained obscure for three decades,ie till 1990s, when theirmode of actionwas found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involvingthevariousenzymes like LCAT (Lecithin-cholesterol acyl transferase)andCYP7A1 etc. (cholesterol 7-alpha-monooxygenase or cytochromeP450 7A1 (CYP7A1)) , transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP,OATP (Na+-dependent taurocholate transporter/ organic anion transporters) . These are the.) andnuclear factors like LXR, PPAR alfa etc. (liver orphan receptorα , and peroxisome proliferative nuclear factor) , in relation to the mechanismsof action of fibrates are discussed . Areas of current interests in literature are briefed.

A novel analytical liquid chromatography-tandem mass spectrometry method for the estimation of Gemfibrozil in bulk and pharmaceutical formulations

The current study reports on a mass spectrometric method for the quantification of gemfibrozil drug substance in itsformulation. Isocratic method was used for separation with help of Zorbax SB C18 column (4.6 × 50 mm, 3 µm) using atriple quadrupole mass detector in multiple reaction monitoring (MRM) mode and electrospray ionization as ionizationsource. The resulting runtime was found to be 3 minutes and the analyte elutes at 1.201 minutes 10-mM ammoniumformate was adjusted to pH 3.5: methanol (20:80 V/V) was used as mobile phase. Increased sensitivity from selectiveion monitoring (SIM) to MRM resulted in decreased quantitation limit (LOQ) and 0.5 ng/ml as detection limit (LOD).The method was validated in a range of 1–50 ng/ml and a correlation coefficient of 0.999. The method recoverywas found to be in the range of 94.03 % to 100.02 %. The developed method was validated as per the InternationalConference on Harmonisation (ICH) guidelines

Reacción adversa a medicamentos (RAM) fija generalizada, debido a gemfibrozilo (GMZ): A propósito de un caso / Case report: generalized fixed drug eruption due to gemfibrozil

El abuso de la ingestión de drogas y la creación de nuevos medicamentos, ha producido un aumento en la aparición de reacción adversa a medicamentos (RAM), los que deben ser siempre informados dada la importancia de su registro. Un tipo de RAM es la erupción fija medicamentosa (EFM). Se revisará un caso de EFM asociada al gemfibrozilo (GMZ) en un paciente chileno de 75 años, quien presentó en dos ocasiones lesiones dermatológicas en la misma localización anatómica, tras la ingestión de GMZ. EFM representa el 5-10% de las RAM y pueden manifestarse en piel y/o mucosas y suelen recurrir en el mismo sitio, cada vez que el paciente consume la droga. Los medicamentos más comunes que producen esta reación son: los antibióticos, analgésicos-anti-inflamatorios no esteroides e hipnóticos. No hemos encontrado publicados casos de EFM a causa de GM. Una EFM ampollar generalizada, es importante diferenciarla clínica e histológicamente del síndrome de Stevens-Johnson o de la necrólisis epidérmica tóxica. Los síntomas, signos, evolución y la histología del caso, nos hace pensar en una EFM bulosa generalizada debido a GMZ.

Biochemical Effects of Some Peroxisome Proliferator Activated Receptor Ligands in Hyperhomocysteinemic-rats.

Hyperhomocysteinemia (HHcy) is implicated in peripheral vascular, cerebrovascular and coronary heart disease. This study was conducted to investigate the effects of pioglitazone (PPAR-γ agonist) and gemfibrozil (PPAR-α agonist), either alone or in combination, in HHcy-rats. HHcy was induced by keeping rats on high methionine diet (8% w/w) for 6 weeks. Rats were divided into two major groups; normal fed rats and methionine overload rats. Each group was further subdivided into four subgroups: a) control group, b) pioglitazone (10 mg/kg), c) gemfibrozil (100 mg/kg), and d) combination of the chosen PPAR ligands. The drugs were given orally daily for consecutive six weeks. The results showed that the great reduction of HHcy was obtained by the drug combination. Induction of HHcy in rats resulted in elevation of LDL-cholesterol and suppression of HDLcholesterol. Hepatic paraoxonase-1 activity was inhibited in all HHcy-rat groups. RT-PCR for liver cyclooxygenase-2 (COX-2) showed marked expression in HHcy-rats, which was attenuated by treatment with PPAR agonists. RT-PCR for cystathionine β-synthase (CBS) showed positive expression in all HHcy-rat groups except that treated with combination of PPAR ligands. These results suggest that pioglitazone-gemfibrozil combination showed ameliorative effect on hyperhomocysteinemia and its consequences in rats.

Effectiveness of lipid-lowering therapy among a sample of patients in Colombia / Eficacia del tratamiento hipolipemiante en una muestra de pacientes de Colombia

OBJECTIVE: To determine the effectiveness of lipid-lowering therapy in a sample of patients affiliated with the Sistema General de Seguridad Social en Salud (the Colombian health system). METHODS: A cross-sectional study was conducted from 1 January 2010-30 June 2011. From a total of 8 316 patients in 10 cities, a random sample of 600 was stratified according to dyslipidemia. Information on sociodemographic and anthropometric characteristics, risk factors, and pharmacological and laboratory variables were obtained from medical records. RESULTS: Subjects were predominantly female (56.2%), with a mean age of 65.1 ± 11.5 years; 93.2% had hypertension; 29.0%, diabetes mellitus; and 10.2%, a history of myocardial infarction. The patients were being treated with lovastatin (84.1%) or gemfibrozil (12.3%)-both at doses below what is recommended-or atorvastatin (1.8%). In patients with high cardiovascular risk, 38.6% achieved goals for low-density lipoprotein cholesterol (LDL-C) levels (<100 mg/dL). Among those at moderate risk, 49.4% reached the target level (< 130 mg/dL). On average, there was a 4.9% reduction in LDL-C. Sex, age, history of cardiovascular disease and/or diabetes mellitus, use of hydrochlorothiazide, and poor therapy adherence were statistically associated with a lack of dyslipidemia control. CONCLUSIONS: Because a lack LDL-C control occurred in patients with two or more of the following variables: male, more than 55 years of age, diabetes and/or a history of cardiovascular disease, received lower doses of lovastatin, or non-adherent to treatment, it is recommended that medication be increased based on clearly-defined therapeutic goals and that comorbidities be assessed and effectively treated.

OBJETIVO: Determinar la eficacia del tratamiento hipolipemiante en una muestra de pacientes afiliados al Sistema General de Seguridad Social en Salud de Colombia. MÉTODOS: Se llevó a cabo un estudio transversal desde el 1 de enero del 2010 al 30 de junio del 2011. De un total de 8 316 pacientes de 10 ciudades seleccionadas, se estratificó una muestra aleatoria de 600 pacientes en función de la dislipidemia. A partir de los expedientes médicos, se obtuvo información sobre las características sociodemográficas y antropométricas, los factores de riesgo y las variables farmacológicas y de laboratorio. RESULTADOS: En la muestra predominaban las mujeres (56,2%) y la media de la edad era de 65,1 ± 11,5 años; 93,2% de los pacientes eran hipertensos; 29,0% eran diabéticos; y 10,2% tenían antecedentes de infarto de miocardio. Los pacientes recibían tratamiento con lovastatina (84,1%) o gemfibrozilo (12,3%) -ambos a dosis inferiores a las recomendadas- o atorvastatina (1,8%). El 38,6% de los pacientes con alto riesgo de enfermedad cardiovascular alcanzaron los objetivos de reducción de los niveles de colesterol unido a lipoproteínas de baja densidad (C-LDL) (< 100 mg/dL). El 49,4% de los pacientes que presentaban un riesgo moderado también alcanzaron los niveles fijados como objetivo (< 130 mg/dL). En promedio, hubo una reducción de 4,9% del C-LDL. El sexo, la edad, los antecedentes personales de enfermedad cardiovascular y diabetes, la administración de hidroclorotiazida y la deficiente adherencia al tratamiento se asociaron estadísticamente con una falta de control de la dislipidemia. CONCLUSIONES: Dado que se produjo un control deficitario del C-LDL en pacientes con dos o más de las siguientes variables: varones, mayores de 55 años, diabéticos o con antecedentes de enfermedad cardiovascular, que recibían dosis bajas de lovastatina, o mostraban falta de adherencia al tratamiento, se recomienda que se aumente la medicación con base en objetivos terapéuticos claramente definidos y que se evalúen y se traten eficazmente las comorbilidades.

Lipid lowering drugs induced adverse cutaneous drug reactions

Background: Lipid lowering drugs (LLDs) are widely used. However, reports on its adverse cutaneous drug reactions (ACDRs) are scarce. Objectives: The study objective was to review the patterns of LLD induced ACDRs. Methods: We reviewed all LLDs induced ACDRs reported to MADRAC (Malaysian Adverse Drug Reaction Advisory Committee) from January 2005 till December 2009. Results: LLD induced ACDRs (124 patients) comprised of 2.07% of all ACDRs reported during the study period. Statins were responsible for most cases (81.5%), followed by fibrates (15.8%), selective cholesterol-absorption inhibitors (1.4%) and combination therapies (statin/selective cholesterol-absorption inhibitors and selective prostaglandin-2 receptor inhibitor/ niacin) in 1.4%. Majority were due to lovastatin (42.5%), simvastatin (28.1%) and gemfibrozil (8.9%). The three commonest ACDRs reported with statins usage were non-specific dermatitis (45.0%), pruritus/stinging (25.0%) and urticaria/angioedema (10.0%) while fibrates caused non-specific dermatitis (52.2%), urticaria/angioedema (13.0%) and photodermatitis (9.7%). There was no reported case of photodermatitis associated with statin usage. Interestingly, statins were the offending drugs resulting in all the five cases of vesiculobullous eruptions, two cases of Stevens-Johnson syndrome and one case of dermatomyositis. No mortalities were reported to be associated with LLD induced ACDRs. Conclusions: LLD induced ACDRs were not uncommon. Statins were the main putative drugs implicated in those reactions. Spectrum of ACDRs differed between statin and fibrate although non-specific dermatitis remained the main ACDRs in both classes. The unavailability of guided and classified ACDRs reporting accounted for the large number of non-specific dermatitis. Although most LLD induced ACDRs were mild, statins were reported to cause severe ACDRs.

Gemfibrozil in Late Preterm and Term Neonates with Moderate Jaundice: A Randomized Controlled Trial.

Objective: To determine, if oral Gemfibrozil is effective in decreasing the duration of phototherapy by at least 24 hours in neonates >34 weeks gestation with nonhemolytic jaundice, as compared to placebo. Design: Double blind placebo controlled randomized controlled trial. Setting: Tertiary care neonatal unit in north India. Subjects: Ninety seven neonates >34 weeks gestation with non-hemolytic jaundice within first 7 days of life requiring phototherapy. Intervention: Two doses of Gemfibrozil (60 mg/kg/dose) or placebo, 12 hours apart. Babies were treated with single surface special blue light phototherapy. Serum total bilirubin (STB) was measured 8 hourly. Phototherapy was stopped if two consecutive STB values were below phototherapy zone. Primary outcome measure: Duration of phototherapy. Results: The median (IQR) duration of phototherapy was 40 (30, 60) hours in Gemfibrozil and 36 (19, 55) hours in the placebo group (P=0.13). The peak STB levels were 16.8 ± 2.7 mg/dL and 16.3 ± 2.3 mg/dL in Gemfibrozil and placebo groups, respectively. No side effect of the drug or placebo was noticed. Conclusion: Two doses of gemfibrozil (60mg/kg/dose) given 12 hours apart were not able to reduce the duration of phototherapy, or peak bilirubin level in babies > 34 weeks gestation with non-hemolytic jaundice in the first week of life. Gemfibrozil was not associated with any side effects.

Respuesta del receptor de lipoproteína de muy baja densidad a estresores inflamatorios / Very low density lipoprotein receptor response to inflammatory stressors

Se estudió la regulación del receptor de lipoproteína de muy baja densidad (VLDLR) en dos tipos de células que intervienen en la respuesta inflamatoria: hepatocitos (HepG2) y células linfocitarias de bazo de ratón (CMB) por agentes implicados en la inflamación: VLDL o Gemfibrozil, lipopolisacárido bacteriano (LPS) para HepG2 o Concanavalina A (ConA) para CMB. Se determinaron por citometría de flujo las subpoblaciones de CMB y de HepG2 en distintas fases del ciclo celular (G1 y G2/M) con ioduro de propidio y las VLDLR+ con VLDL fluorescente. Entre 10 a 60 por ciento de células expresaron VLDLR dependiendo de las condiciones experimentales. El enfrentamiento con LPS o ConA produjo un aumento de células VLDLR+. El tratamiento con Gemfibrozil disminuyó el número de hepatocitos en reposo VLDLR+ pero incrementó significativamente (más de dos veces) los hepatocitos VLDLR+ en fase G2/M. En los cultivos de CMB Gemfibrozil aumentó por igual el porcentaje de células VLDLR+ quiescentes y en G2/M. El comportamiento de estos tipos celulares con VLDL fue distinto: CMB no mostró cambios en las subpoblaciones VLDLR+, los hepatocitos mostraron disminución de VLDLR+ tanto en fase G1 como en fase G2/M. Se concluyó que el estudio de la regulación de VLDLR en distintas células facilitará el diseño de fármacos específicos para el tratamiento de enfermedades de etiología inflamatoria.

The regulation of the VLDL receptor (VLDLR) by molecules involved in the inflammation process (lipopolysaccharide, LPS; Concanavalin A, ConA, VLDL or Gemfibrozil) in two cellular types implied in the inflammatory response, hepatocytes (HepG2) and lymphocitary cells from mice spleen (CMB), was studied. Different subpopulations of CMB and HepG2 in different cell cycle phases (G1 and G2/M) were analyzed using flow citometry techniques with propidium iodide, and the VLDLR+ with fluorescent VLDL. In cultures of both cell types, it was observed that 10 to 60% of the cells expressed the VLDLR (VLDLR+ cells) indistinctly of the culture conditions. VLDLR+ cells belonged equally to cells in the quiescent and in the synthesis or mitosis phase of the cell cycle. Challenging them with LPS or ConA an increase in the percentage of VLDLR+ cells was produced. Gemfibrozil treatment decreased the number of resting hepatocytes VLDLR+ but increased significantly (more than twice) the number of hepatocytes VLDLR+ in phase G2/M. In hepatocytes there was almost the same proportion of VLDLR+ cells that were in the G1 or in the G2/M phase of the cell cycle. It is concluded that the study of VLDLR regulation will facilitate the design of new drugs to treat inflammatory diseases.

Effect of Fibrate on Lipoprotein(a) Level in Hypertriglyceridemic Patients

BACKGROUND AND OBJECTIVES: The responses of lipoprotein (a) [Lp(a)] to lipid-lowering drugs are different from those of other lipids and lipoproteins. Most reports on the effect of fibrate on the Lp (a) level have only a few cases, with inconsistent results. This study was designed to evaluate the effect of fibrate on the Lp (a) level in hypertriglyceridemic patients. SUBJECTS AND METHODS: Patients with either a triglyceride (TG) level over 300mg/dL or TG level over 200mg/dL and a high density lipoprotein cholesterol level below 40mg/dL, were enrolled. They were treated with either fibrate (Fibrate group, n=29) or general measures (Control group, n=29). Gender and age matched patients with hypercholeste-rolemia were adopted and treated with statin (Statin group, n=29). The lipid and lipoprotein levels were measured before and after the medication for 2 months. RESULTS: The baseline Lp (a) levels were similar between the Fibrate and Control groups (p=0.19). Fibrate therapy increased the Lp (a) level from 10.3+/-16.4 to 15.1+/-15.2 mg/dL (p=0.003), but there were no changes in the Lp (a) levels in the Statin and Control groups. Before the treatment, the Lp (a) levels were negatively associated with the TG levels (r=-0.36, p=0.001). The relationship became weaker and insignificant after the medication. The more the TG level was decreased, the more the Lp (a) level was increased in all of the cases (r=-0.35, p=0.001 ) as well as in the Fibrate group (r=-0.46, p=0.013). CONCLUSION: Fibrate increased the Lp (a) level, and this elevation was associated with the reduction in the TG level. This finding might be related with a lesser cardioprotective effect of fibrate than that of statin in addition to the effect on the cholesterol level.

Recurrent Rhabdomyolysis after Cerivastatin-Gemfibrozil Combination Therapy / 대한신장학회잡지

A 64-year-old woman with ischemic heart disease was admitted to our hospital because of both leg pain and difficulty to walk for 5 days. She had taken cerivastatin and gemfibrozil for atherosclerosis and ischemic heart disease. One year ago, she had been admitted to our hospital because of acute renal failure due to rhabdomyolysis of unknown origin and was improved after conservative therapy. Laboratory studies revealed serum creatinine 1.2 mg/dL, creatine kinase 23,700 IU/L, serum myoglobin >500 ng/mL, urine myoglobin >3,000 ng/mL. (99m)Tc-HDP whole body Bone scan showed multiple increased uptakes of the soft tissue, especially both calf. With supportive care, she was recovered and discharged with normal creatinine(0.8 mg/dL) and creatine kinase(260 IU/L).

Studies on the Bioequialence of Two Preparations of Gemfibrozil / 中国药房

OBJECTIVE:To evaluate the bioequivalence of two preparations of gemfibrozil.METHODS:A single oral dose of gemfibrozil enteric capsule(test preparation)and capsule(reference preparation)was given to20volunteers in an open ran?domized crossover way to study the pharmacokinetics and relative bioavailability.The plasma gemfibrozil concentrations were determined by HPLC method.RESULTS:The pharmacokinetic parameters of test and reference preparations were as follows:T max ,(2.4?0.6)h and(2.3?0.7)h;C max ,(21.8?7.3)?g/ml and(23.7?5.9)?g/ml;T 1/2 ,(2.0?0.4)h and(2.0?0.5)h;AUC 0～12 ,(68.1?13.7)(?g?h)/ml and(68.9?17.4)(?g?h)/ml;AUC 0～∞ (69.7?13.9)(?g?h)/ml and(70.6?17.8)(?g?h)/ml respectively.The relative bioavailability of test preparation was(100.8?15.0)%.The result of statistical analysis on above parameters showed that there was no significant difference between two preparations.CONCLUSION:The two prepa?rations were bioequivalent.

Rhabdomyolysis Associated with Cerivastatin-Gemfibrozil Combination Therapy: 1 case

Most currently available statins are associated with an increase with risk of myositis, including rhabdomyolysis. Myopathy is believed to be caused by interference in the cytochrome P450 3A4 enzyme system, which results in a marked increase in reductase activity. Cerivastatin, a new synthetic HMG-CoA reductase inhibitor, is a safe, well-tolerated effective drug for the treatment of patients with dyslipidemia. The drug is metabolized by the cytochrome P450 3A4 and cytochrome P450 2C8 hepatic isoenzymes. Because of this dual metabolic pathway, it has been suggested that cerivastatin is less subject to drug-todrug interactions. We describe a 60-year-old woman with rhabdomyolysis and localized myositis, after she had taken cerivastatin(lipobay, 0.3 mg/day) and gemfibrozil(lopid, 500 mg/day) for 1month.

Pharmacokinetics and relative bioavailability of gemfibrozil capsules in 12 healthy volunteers / 中国临床药理学与治疗学

Aim The pharmacokinetic parameters and relative bioavailability of capsule A(Maiwei Pharmaceutical Co Ltd, Beijing, China) and capsule B (Xianjing Pharmaceu-tical, Hunan, China) were studied. Methods A single oral dose of 600 mg gemfibrozilof these two kinds of capsules was given to 12 chinese healthy male volunteers in anopen, randomized crossover study. Plasma levels were determined with HPLC-UVmethod. Results The plasma concentration-time curve was fitted to 1-compartmentopen model with a first order and lag time absorption and the major pharmacokineticparameters of capsules A and B were shown respectively as following: C max(32. 69?5. 67 )and (29. 41?2. 60) mg?L-1; Tmax (1. 01?0. 14) and (1. 13?0. 37) h, t1/2ka(0. 46 ? 0. 18) and (0. 62 ? 0. 20) h; C max (1. 11 ? 0. 32) and (1. 32 ? 0. 26) h; MRT(2. 14 ? 0.27) and (2. 37 ? 0.26) h; AUC (91.7 ? 13.2) and (82.2 ? 7. 38) mg?h? L-1. There were no significantly differences between the pharmacokinetic parame-ters of capsule A and B. The relative bioavailability of the capsule A was (110 ? 9) % ascompared to the capsule B. Conclusion The two kinds of capsules have the equivalentbiological effects.

Estudo comparativo do gemfibrozil versus pravastatina no tratamento de portadores de doença arterial coronária e níveis reduzidos de HDL-colesterol / Comparative study of gemfibrozil versus pravastatin in the treatment of patients with coronary artery disease and low HDL cholesterol levels

PURPOSE--To evaluate the effects of gemfibrozil and pravastatin in coronary artery disease patients with HDL-cholesterol (HDL-C) < 35 mg/dl). METHODS--Twenty-nine patients (20 males, 60 +/- 9) were divided in a gemfibrozil group (G) (1200 mg/day n = 15) and a pravastatin group (P) (10 or 20 mg n = 10 and 4, respectively). The plasma lipid profile (LP) e.g. total cholesterol (TC), fractions and triglycerides (TG) was determined at 4 and 12 weeks of treatment. RESULTS--HDL-C was not affected in P, TC and LDL-cholesterol (LDL-C) reductions were superior to those in G (31.3 vs 13.4 and 38.7 and 11.5, p < 0.05 and < 0.01 respectively). In G HDL-C raised by 50 (12th week p < 0.01). Gemfibrozil reduced TG levels in 44.7 while in P it varied -32.2 (12th week p < 0.01 and < 0.05 respectively). CONCLUSION--Gemfibrozil is more effective in reducing TG and raising HDL-C than pravastatin. On the other hand, pravastatin was more potent in reducing LDL-C levels.

Objetivo - Comparar os efeitos do gemfibrozil e pravastatina no perfil lipídico (PL) de pacientes coronarianos com HDL-colesterol (HDL-C) <35 mg/dl Métodos - Vinte e nove pacientes (20 homens, 60 9 anos) divididos em grupo gemfibrozil (G) (1200mg/dia n=15) e grupo pravastatina (P) (10mg e 20mg, 10 e 4 pacientes, respectivamente). O perfil lipídico plasmático [colesterol total (CT), frações e triglicérides (TG)] foi avaliado a 4 e 12 semanas de tratamento. Resultados - Em P, o HDL-C não se alterou, as reduções de CT e LDL-colesterol (LDL-C) foram superiores às de G (31,3% vs 13,4% e 38,7 e 11,5%, respectivamente p<0,05 e <0,01). Em G. o HDL-C elevou-se em até 50% (12º semana, p<0,01). O gemfibrozil reduziu os TG em 44,7% (p<0,01) enquanto que em P, a variação foi de -32,2% na 12º semana (p<0,05). Conclusão - O gemfibrozil é mais eficaz que a pravastatina para reduzir os TG e elevar o HDL-C, porém a pravastatina é um redutor mais potente do LDLC

Comparação entre lovastatina e o gemfibrozil no tratamento de hiperlipidemias primárias / Comparison between lovastatin and gemfibrozil in treatment of primary hyperlipidemias

Purpose - To compare the effects of lovastatin and gemfibrozil in patients with primary hyperlipidemias. Patients and Methods - Forty patients with cholesterolemia over 200 mgldl and triglyceridemia not higher than 350 mp/dl, excluded secondary causes, were selected. Twenty patients received lovastatin and 20 gemfibrozil. In order to establish the lipid profile, blood samples were taken after 2 months without medication, after 4 weeks of diet and placebo and after 6 and 12 weeks active treatment. Biochemic profile was determined before and after the treatment with active drug. Results - Thirty nine patients completed the study. Total and LDL-cholesterol were significantly reduced (p < 0.05) by both drugs but lovastatin had greater effect. Only gemfibrozil reduced triglycerides significantly. Neither drug had significant effects on HDL-cholesterol. The tolerance was satisfactory; only one patient (using gemfibrozil) needed to stop the treatment due to gastrointestinal side effects. The biochemic profïle did not present any significant alteration. Conclusion - Both drugs produced useful effects on the lipid profile. Lovastatin produced greater reductions of total and LDL-cholesterol, while gemfibrozil was more active reducing triglycerides. Neither drug changed significantly the HDL-cholesterol

Lipid-regulators and myopathy, rhabdomyolysis / 中国药理学通报

It is reported that lipid-regulators including statins, nicotinic acid and fibrates can induce severe adverse reactions such as myopathy, even rhabdomyolysis which endangers the patient's life. The authors have discussed the relationship between lipid-regulators and myopathy, rhabdomyolysis, how those drugs cause these adverse reactions and the major factors for myopathy and rhabdomyolysis in order to deepen the knowledge, prevent the happenness of these diseases and develop the more effective and safer lipid-regulators.