Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new lopid research articles will be listed here shortly after becoming available to us.
Related Sponsors
Medical research on lopid
Enferm Infecc Microbiol Clin. 2008 Jun; 26(6): 325-9
Bottaro EG, Caravello O, Scapellato PG, Stambulian M, Vidal GI, Loggia V, Scapellato JL, Thompson F, Cassetti I
INTRODUCTION: Highly active antiviral therapy (HAART) results in a sharp decrease in HIV-related morbidity and mortality, but also induces adverse effects such as dyslipidemia, which is difficult treat because of drug interactions. Guidelines recommend lipid-lowering therapy with pravastatin or atorvastatin to reduce LDL cholesterol in these patients, and gemfibrozil or fenofibrate for treating hypertriglyceridemia. The use of statins in the management of dyslipidemia is complicated by drug interactions with some of the components of HAART. Rosuvastatin, a statin with minimal cytochrome P-450-mediated metabolism, could be an alternative option for this population. METHODS: Retrospective study to evaluate the efficacy and safety of rosuvastatin (10 mg/day) for 16 weeks in HAART-treated HIV-infected patients with dyslipidemia, and moderate to high cardiovascular risk. Results were analyzed with the Shapiro-Wilks, K-S Lilliefors, and sign tests. Percentages were analyzed with the chi-square test. RESULTS: Seventy-eight patients were started on rosuvastatin for dyslipidemia, 60 as single therapy. After 16 weeks of treatment, a significant median decrease was seen in both LDL-cholesterol and non-HDL cholesterol (31.3% reduction in LDL and 29.9% in non-HDL). The therapeutic goal for non-HDL was achieved in 65.8% of patients. The decrease in triglyceride levels was also significant (34.1%); 35% of subjects achieved the therapeutic goal. The drug was withdrawn in 2 patients because of myositis, and in 1 because of gastrointestinal intolerance. There were no differences in efficacy or toxicity between patients receiving protease inhibitors, non-nucleoside reverse transcriptase inhibitors, or fibrates. CONCLUSION: Rosuvastatin was safe and effective for treating dyslipidemia in HAART-treated HIV-infected patients. Results were similar to those observed in the HIV-uninfected population.
Steroids. 2008 Jun 6;
Bertolotti M, Del Puppo M, Gabbi C, Corna F, Carulli L, Pellegrini E, Zambianchi L, Anzivino C, Ricchi M, Loria P, Kienle MG, Carulli N
BACKGROUND/AIM: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7alpha-hydroxy-4-cholesten-3-one have been reported to reflect bile acid synthesis and the expression or activity of the limiting enzyme of the main biosynthetic pathway, cholesterol 7alpha-hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7alpha-hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. DESIGN: Concentrations of 7alpha-hydroxy-4-cholesten-3-one were assayed by gas-liquid chromatography: mass spectrometry in plasma samples obtained in 18 patients with primary hyperlipoproteinemia who previously underwent determination of cholesterol 7alpha-hydroxylation rates in vivo by tritium release analysis. Both determinations were performed in basal conditions and after treatment with hypolipidemic drugs (the fibric acid derivatives gemfibrozil and bezafibrate, cholestyramine alone or associated with simvastatin). RESULTS: Changes in plasma 7alpha-hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7alpha-hydroxylation rates during treatment with fibrates, cholestyramine and cholestyramine plus simvastatin. When plotting determinations from all studies (n=40), a very strict correlation was disclosed between plasma 7alpha-hydroxy-4-cholesten-3-one and cholesterol 7alpha-hydroxylation rates (r=0.81, P
Polim Med. 2007; 37(4): 21-38
Zgoda MM, Nachajski MJ, Kołodziejczyk MK, Woskowicz MH, Lukosek M
Research was conducted into the properties and identity of the products of oxyethylation of cholic acid, which were obtained with the use of a selective catalyst (K4). The 1HNMR method was employed to assess the content of oxyethylated segments and the analytic level of hydrophilic-lipophilic balance (HLB). Surface activity of the products of oxyethylation in water and 0.1 M HCL was examined and cmc and gamma(25)cmc were determined. These were employed to calculate the thermodynamic potential for micelle formation deltaG(o)m and the surface occupied by the lipophilic structure of the surfactant at the phase boundary. Basic viscosity and hydrodynamic values were determined for the solubilizers and their micellar adducts with diclofenac, ketoprofen, fenofibrate, gemfibrozil and nifedipine. In addition, the amount of solubilized therapeutic agents c/s/ was examined by means of the spectroscopic method and the H/L balance in a solid state. The results obtained in the course of research served as a basis for determining the solubilization mechanism and the stability of the micellar adduct for the purpose of application.
Clin Pharmacokinet. 2008; 47(7): 463-74
Neuvonen PJ, Backman JT, Niemi M
HMG-CoA reductase inhibitors (statins) dose-dependently lower both the level of low-density lipoprotein cholesterol and risk of cardiovascular disease. In 2004, the UK approved a low-dose over-the-counter (OTC) simvastatin, but the US has rejected applications for non-prescription preparations of statins. The pharmacokinetics and interaction potentials of the possible OTC candidate statins simvastatin, lovastatin, fluvastatin and pravastatin are clearly different. Simvastatin and lovastatin are mainly metabolized by cytochrome P450 (CYP) 3A, fluvastatin is metabolized by CYP2C9, and pravastatin is excreted largely unchanged. Several cell membrane transporters can influence the disposition of statins, e.g. the organic anion transporting polypeptide (OATP) 1B1 enhances their hepatic uptake. The c.521T>C (p.Val174Ala) genetic polymorphism of SLCO1B1 (encoding OATP1B1) considerably increases the plasma concentrations of simvastatin acid and moderately increases those of pravastatin but seems to have no significant effect on fluvastatin. Strong inhibitors of CYP3A (itraconazole, ritonavir) greatly (up to 20-fold) increase plasma concentrations of simvastatin, lovastatin and their active acid forms, thus enhancing the risk of myotoxicity. Weak or moderately potent CYP3A inhibitors such as verapamil, diltiazem and grapefruit juice can be used cautiously with low doses of simvastatin or lovastatin, but their concomitant use needs medical supervision. Potent inducers of CYP3A can greatly decrease plasma concentrations of simvastatin and simvastatin acid, and probably those of lovastatin and lovastatin acid. Although fluvastatin is metabolized by CYP2C9, its concentrations are changed less than 2-fold by inhibitors or inducers of CYP2C9. Pravastatin plasma concentrations are not significantly affected by any CYP inhibition and only slightly affected by inducers. Ciclosporin inhibits CYP3A, P-glycoprotein and OATP1B1. Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. Ciclosporin and gemfibrozil increase plasma concentrations of statins and the risk of their myotoxicity, but fluvastatin seems to carry a smaller risk than other statins. Inhibitors of OATP1B1 may decrease the benefit-risk ratio of simvastatin, lovastatin and pravastatin by interfering with their (active acid forms) entry into hepatocytes. Understanding the differences in the pharmacokinetics and interaction potential of various statins helps in their selection for possible non-prescription status. On the pharmacokinetic basis, fluvastatin and pravastatin can be better choices than simvastatin or lovastatin for an OTC statin.
Plasma PCSK9 levels are significantly modified by statins and fibrates in humans.
Lipids Health Dis. 2008; 7: 22
Mayne J, Dewpura T, Raymond A, Cousins M, Chaplin A, Lahey KA, Lahaye SA, Mbikay M, Ooi TC, Chrétien M
BACKGROUND: Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men. RESULTS: Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either. CONCLUSION: These results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.
The effects of pharmaceuticals on the regeneration of the cnidarian, Hydra attenuata.
Sci Total Environ. 2008 Aug 25; 402(1): 62-9
Quinn B, Gagné F, Blaise C
The Hydra attenuata regeneration assay was used to identify the teratogenic potential of 10 pharmaceuticals identified in effluent from a large city wastewater treatment plant (WWTP). Three types of solvents were used to solubilise the pharmaceuticals (DMSO, acetone and ethanol), at concentrations determined to have no significant effect on measured endpoints. On the one hand, regeneration was significantly inhibited at (nominal) concentrations of 1, 5 and 1 mg/L for gemfibrozil, ibuprofen and naproxen respectively and at the higher concentration of 50 mg/L for bezafibrate and trimethoprim. On the other hand, carbamazepine and the antibiotics sulfapyridine, oxytetracycline and novobiocin significantly increased regeneration at 25, 5, 50 and 50 mg/L respectively. Relatively high IC(50) values of 0.9, 3.84, 4.9 and 22.5 mg/L were calculated for gemfibrozil, ibuprofen, naproxen and bezafibrate, respectively. However when subjected to tier two toxicity assessment under EU regulatory guidance using environmentally relevant concentrations a MEC/PNEC value>1 was calculated for gemfibrozil, ibuprofen and naproxen indicating teratogenic potential and the necessity for further tier three assessment. A toxicity index (TI) was also calculated using three different techniques, with TI values>3 (indicating teratogenic potential) found for gemfibrozil, ibuprofen, naproxen and bezafibrate and >1 (indicating a weak teratogenic potential) found for carbamazepine. These results are discussed in the context of their environmental relevance and toxic potential.
Proc Natl Acad Sci U S A. 2008 Jun 10; 105(23): 8091-6
Zheng BJ, Chan KW, Lin YP, Zhao GY, Chan C, Zhang HJ, Chen HL, Wong SS, Lau SK, Woo PC, Chan KH, Jin DY, Yuen KY
The mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4+ and CD8+ T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.
Combination statin-fibrate therapy: safety aspects.
Diabetes Obes Metab. 2008 Jun 1;
Franssen R, Vergeer M, Stroes ES, Kastelein JJ
Patients with type 2 diabetes or metabolic syndrome remain at high residual risk of cardiovascular events even after intensive statin therapy. While treatment guidelines recommend the addition of a fibrate to statin therapy in this setting, concerns about the potential for myopathy may limit the use of this combination in clinical practice. These concerns are certainly justified for gemfibrozil, which interferes with statin glucuronidation, leading to elevation in statin plasma concentrations and an increased risk of myotoxicity in combination with a range of commonly prescribed statins. However, the available evidence refutes suggestions that this is a class effect for fibrates. Fenofibrate does not adversely influence the metabolism or pharmacokinetics of any of the commonly prescribed statins. This in turn translates to a reduced potential for myotoxicity in combination with a statin. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the efficacy and safety of fenofibrate plus simvastatin combination therapy in type 2 diabetes patients.
Prostaglandins Leukot Essent Fatty Acids. 2008 Apr-May; 78(4-5): 271-80
Nyalala JO, Wang J, Dang A, Faas FH, Smith WG
The effect of atorvastatin, simvastatin and gemfibrozil on fatty acid composition of plasma phospholipids (PL), cholesterol esters (CE), triglycerides (TG) and red cell membrane ghosts (G) has been determined in appropriate sample populations of individuals with hypertriglyceridemia (HTG) or hypercholesterolemia (HCHL). Treatments were appropriate for the condition, gemfibrozil for HTG and a statin for HCHL. Modifications depend on the drug and lipid fraction examined. Both classes of drugs modify fatty acid composition but gemfibrozil modifications are more numerous and dramatic than are the modifications by statins. Gemfibrozil produces major modifications in fatty acid composition, which are both fatty acid and lipid class specific but generally decreases SFA and increases PUFA (mainly n6) and increases the proportion of fatty acids with chain length of 18C or more. Statins tend to increase chain length but have less effect on saturation. Notably, all three drugs increased arachidonic acid (AA) in PL and CE. Statins decreased gamma-linoleic acid (GLA) in PL and CE but gemfibrozil only increased GLA in TG.
Micronization of gemfibrozil by reactive precipitation process.
Int J Pharm. 2008 Apr 22;
Huang QP, Wang JX, Chen GZ, Shen ZG, Chen JF, Yun J
Ultrafine gemfibrozil (GEM) was prepared by reactive precipitation process in which methyl cellulose (MC) was employed to inhibit the growth and the agglomeration of particles. The impact of NaOH concentrations on bulk GEM consumption was explored. The effects of H(2)SO(4) concentrations and the drying methods on the particle size and morphology were also discussed. The produced ultrafine powders were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, specific surface area analysis and dissolution test. XRD patterns and FT-IR spectra showed that the as-obtained ultrafine GEM was a crystalline powder with the structure and components similar to those of bulk GEM. The ultrafine GEM had a mean particle size of about 1.25mum with a narrow distribution from 0.6 to 3mum. The specific surface area reached up to 11.01m(2)/g, which was about 6 times as large as that of bulk GEM. In the dissolution tests, about 91.2% of ultrafine GEM was dissolved after 120min, while there was only 23.6% of bulk GEM dissolved, proving that the dissolution property of ultrafine GEM was significantly enhanced when compared to commercial GEM owing to a decreased particle size and an increased specific surface area.