Lipoprotein composition and oxidative modification during therapy with gemfibrozil and lovastatin in patients with combined hyperlipidaemia.

Abstract:

AIM:To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. METHODS:VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation related analytes after Cu-induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composition, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar composition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been studied. RESULTS:Both drugs reduced the plasma concentration of apo-B lipoproteins (-23% gemfibrozil, -26% lovastatin), but whereas lovastatin affected mainly LDL-cholesterol (-30%), gemfibrozil reduced triglycerides (-49%) and VLDL-cholesterol (-48%). Lovastatin treatment had no effect on the lipid and protein composition, the fatty acid profile, or the vitamin E content of either VLDL or LDL; likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes, thiobarbituric acid reactive substances formation, and lysine residues) were similar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL-triglycerides (-32%), and b) increased the proportion (molar%) of 18:3 n-6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl esters (+53%). CONCLUSIONS:Based on these results, lovastatin and gemfibrozil do not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia. In the case of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty acids in VLDL. In the context of a fixed dietary intake, such modifications suggest that the drug influences liver enzyme activities involved in fatty acid chain synthesis (elongases and desaturases).

journal_name

Br J Clin Pharmacol

authors

Vázquez M,Zambón D,Hernández Y,Adzet T,Merlos M,Ros E,Laguna JC

doi

10.1046/j.1365-2125.1998.00672.x

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

265-9

issue

3

eissn

0306-5251

issn

1365-2125

journal_volume

45

pub_type

临床试验,杂志文章,随机对照试验
  • Dynamic population pharmacokinetic-pharmacodynamic modelling and simulation supports similar efficacy in glycosylated haemoglobin response with once or twice-daily dosing of canagliflozin.

    abstract:AIM:Canagliflozin is an SGLT2 inhibitor approved for the treatment of type-2 diabetes. A dynamic population pharmacokinetic-pharmacodynamic (PK/PD) model relating 24-h canagliflozin exposure profiles to effects on glycosylated haemoglobin was developed to compare the efficacy of once-daily and twice-daily dosing. METH...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcp.13180

    authors: de Winter W,Dunne A,de Trixhe XW,Devineni D,Hsu CH,Pinheiro J,Polidori D

    更新日期:2017-05-01 00:00:00

  • Social media and pharmacovigilance: A review of the opportunities and challenges.

    abstract::Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges rem...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bcp.12717

    authors: Sloane R,Osanlou O,Lewis D,Bollegala D,Maskell S,Pirmohamed M

    更新日期:2015-10-01 00:00:00

  • The haemodynamic effects of subcutaneous sumatriptan, a 5HT1-receptor agonist.

    abstract:AIMS:Previous in vivo studies with sumatriptan, a 5HT1-receptor agonist, have demonstrated vasopressor responses in the pulmonary and systemic arterial circulation. Pulmonary artery wedge pressure (PAWP) also increases after sumatriptan injection, raising the possibility of an additional venoconstrictive action or a ne...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1997.00555.x

    authors: Hood S,Birnie D,Hillis S

    更新日期:1997-03-01 00:00:00

  • Development of AITC-induced dermal blood flow as a translational in vivo biomarker of TRPA1 activity in human and rodent skin.

    abstract:BACKGROUND AND PURPOSE:Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. EXPERIMENTAL APPROACH:Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1-knock out (Trpa1 KO) rats, and changes ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.14370

    authors: Joseph V,Yang X,Gao SS,Elstrott J,Weimer RM,Theess W,Thrasher C,Singh N,Lin J,Bauer RN

    更新日期:2021-01-01 00:00:00

  • Effects of food and exercise on the absorption of effervescent aspirin.

    abstract::1 The absorption of effervescent aspirin was studied in normal volunteers of both sexes under varied conditions of activity in both fasting and non-fasting states. 2 Moderate activity resulted in no significant changes in absorption compared with that at rest. 3 In non-fasting subjects the absorption was reduced but t...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1974.tb00222.x

    authors: Volans GN

    更新日期:1974-04-01 00:00:00

  • A study of nadolol to determine its effect on ambulatory blood pressure over 24 hours, and during exercise testing.

    abstract::1 The effect of once daily nadolol therapy in sixteen ambulant patients with essential hypertension has been closely assessed during exercise and over 24 h by continuous intra-arterial recording. 2 The drug was well tolerated and showed similar efficacy to other beta-adrenoceptor blocking agents. Whilst blood pressure...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1982.tb04938.x

    authors: Hornung RS,Gould BA,Kieso H,Raftery EB

    更新日期:1982-07-01 00:00:00

  • The epidemiology of self-poisoning in the UK.

    abstract::Self-poisoning by ingestion or inhalation is common, and it is important to study its various epidemiological manifestations with clear definitions. Data on fatal self-poisonings are recorded nationally within the UK and are codified according to the International Classification of Diseases (ICD) revision relevant at ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2125.2003.01910.x

    authors: Camidge DR,Wood RJ,Bateman DN

    更新日期:2003-12-01 00:00:00

  • Have COX-2 inhibitors influenced the co-prescription of anti-ulcer drugs with NSAIDs?

    abstract:AIMS:To quantify usage of COX-2 inhibitors compared with nonselective NSAIDs and to determine their impact (including financial) on the co-prescription of antipeptic ulcer (anti-PU) drugs. METHODS:The Irish General Medical Services prescription database (covering 1.2 million people) was examined for NSAID prescription...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2125.2003.02012.x

    authors: Teeling M,Bennett K,Feely J

    更新日期:2004-03-01 00:00:00

  • Limited predictability of amikacin clearance in extreme premature neonates at birth.

    abstract:AIM:Identify and quantify factors describing variability of amikacin clearance in preterm neonates at birth. METHODS:Population pharmacokinetics of amikacin were estimated in a cohort of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24-30 weeks; weight 1.07, SD 0.34, range 0.45-1.98 kg, p...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2005.02530.x

    authors: Allegaert K,Anderson BJ,Cossey V,Holford NH

    更新日期:2006-01-01 00:00:00

  • Efficacy, safety and pharmacokinetics of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control.

    abstract:AIMS:The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. METHODS:Three clinical studies were performed. First, 16 healthy subject...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcp.14076

    authors: Wang H,Shao F,Liu X,Xu W,Ou N,Qin X,Liu F,Hou X,Hu H,Jiang J

    更新日期:2019-11-01 00:00:00

  • Possible association between ocular chloramphenicol and aplastic anaemia--the absolute risk is very low.

    abstract:AIMS:To determine whether topical ocular chloramphenicol increases the risk of aplastic anaemia and to estimate the magnitude of this risk, if any. METHODS:Population-based prospective case-control surveillance of aplastic anaemia in a community of 4.2 million inhabitants from 1980 to 1995 (67.2 million person-years) ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2125.1998.00773.x

    authors: Laporte JR,Vidal X,Ballarín E,Ibáñez L

    更新日期:1998-08-01 00:00:00

  • Bioavailability of the antiemetic metopimazine given as a microenema.

    abstract::The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite were measured. The bio...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1046/j.1365-2125.1996.35220.x

    authors: Herrstedt J,Jørgensen M,Angelo HR,Rassing MR,Møller-Sonnergaard J,Dombernowsky P

    更新日期:1996-06-01 00:00:00

  • Sulphate conjugation of beta 2-adrenoceptor stimulating drugs by platelet and placental phenol sulphotransferase.

    abstract::A possible route of metabolism of beta-adrenoceptor stimulating drugs used in obstetrics consists of conjugation by the enzyme phenol sulphotransferase. The substrate specificities of the platelet and the placental enzymes towards these drugs were tested. The specific activities of the beta-adrenoceptor agonists were ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1984.tb05009.x

    authors: Sodha RJ,Schneider H

    更新日期:1984-01-01 00:00:00

  • Does smoking influence the pharmacokinetics and pharmacodynamics of the H2-receptor antagonist famotidine?

    abstract::Twelve healthy habitual cigarette smokers and eight non-smokers participated in a double-blind placebo controlled study to determine the effect of smoking on the pharmacokinetics and pharmacodynamics of the H2-receptor antagonist famotidine. In smokers, cigarette smoking was standardised and started 1 h before (A), or...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1992.tb04025.x

    authors: Baak LC,Ganesh S,Jansen JB,Lamers CB

    更新日期:1992-02-01 00:00:00

  • Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin.

    abstract:AIMS:To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS:Continuous radial pulse wave analysis, whole-body impedance cardiograp...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2009.03434.x

    authors: Tahvanainen A,Leskinen M,Koskela J,Ilveskoski E,Alanko J,Kähönen M,Kööbi T,Lehtimäki L,Moilanen E,Mustonen J,Pörsti I

    更新日期:2009-07-01 00:00:00

  • The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet.

    abstract::1. Since salt depletion stimulates the renal prostaglandin system to maintain renal function, the effects of indomethacin and ibuprofen upon renal haemodynamics, electrolyte excretion and renin release were examined in eight healthy male volunteers on a salt restricted diet, before and after frusemide administration. ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1990.tb03641.x

    authors: Passmore AP,Copeland S,Johnston GD

    更新日期:1990-03-01 00:00:00

  • Atenolol elimination in the neonate.

    abstract::The elimination of the cardioselective beta-adrenoceptor antagonist atenolol has been studied in 35 neonates by measuring drug concentration in cord blood and in blood obtained at 24 h by heel stab. Elimination rate was assessed by calculating the slopes of lines joining these two concentration points. The slopes had ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1983.tb02237.x

    authors: Rubin PC,Butters L,Reynolds B,Evans J,Sumner D,Low RA,Reid JL

    更新日期:1983-12-01 00:00:00

  • A free lignocaine index as a guide to unbound drug concentration.

    abstract::A free lignocaine index was developed on the basis of measurements of plasma lignocaine and its principle binding protein, alpha 1-acid glycoprotein (AAG) in 80 samples from 16 patients admitted to the coronary care unit and given prophylactic lignocaine therapy. The free drug fraction, fu, of lignocaine was determine...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1985.tb05132.x

    authors: Routledge PA,Lazar JD,Barchowsky A,Stargel WW,Wagner GS,Shand DG

    更新日期:1985-12-01 00:00:00

  • Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers.

    abstract::1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.1994.tb04268.x

    authors: Harrison RW,Ashton CH

    更新日期:1994-03-01 00:00:00

  • Drug resistance, inappropriate dosing and non-compliance in hypertensive patients.

    abstract::1 From an understanding of the biological fate and hypotensive effect of debrisoquine (D) we have assessed the relative importance of true drug resistance, inappropriately low dosage and non-compliance as causes of apparent resistance to treatment with this drug. 2 Among 37 hypertensive patients prescribed D, eleven (...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1980.tb01072.x

    authors: Silas JH,Tucker GT,Smith AJ

    更新日期:1980-04-01 00:00:00

  • Inhibition of paracetamol glucuronidation by tyrosine kinase inhibitors.

    abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• Clinical cases reported that fatal acute liver failure occurred when paracetamol (acetaminophen) was co-administrated with some tyrosine kinase inhibitors (TKIs). The direct inhibition of UDP-glucuronosyltransferase activities has been identified as a mechanism of potentiation...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2011.03911.x

    authors: Liu Y,Ramírez J,Ratain MJ

    更新日期:2011-06-01 00:00:00

  • Bioactivity of enoxaparin in critically ill patients with normal renal function.

    abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes. Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2012.04285.x

    authors: Gouya G,Palkovits S,Kapiotis S,Madl C,Locker G,Stella A,Wolzt M,Heinz G

    更新日期:2012-11-01 00:00:00

  • Plasma concentrations and protein binding of disopyramide and mono-N-dealkyldisopyramide during chronic oral disopyramide therapy.

    abstract::1 The plasma levels of disopyramide and mono-N-dealkyldisopyramide were measured from 118 patients, and the protein binding of both drugs from 50 patients during chronic oral disopyramide therapy. 2 No significant correlation was seen between the daily dose of disopyramide and the achieved plasma drug concentration. 3...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1981.tb01134.x

    authors: Aitio ML

    更新日期:1981-04-01 00:00:00

  • Effect of candesartan, a type 1 angiotensin II receptor antagonist, on bronchial hyper-responsiveness to methacholine in patients with bronchial asthma.

    abstract:AIMS:Angiotensin II is a putative mediator in bronchial asthma. There have been very few studies investigating the involvement of angiotensin II receptors in bronchial hyper-responsiveness in asthmatic patients. We examined the effect of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist,...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1046/j.1365-2125.2002.t01-4-01689.x

    authors: Myou S,Fujimura M,Kamio Y,Kita T,Watanabe K,Ishiura Y,Hashimoto T,Nakao S

    更新日期:2002-12-01 00:00:00

  • Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers--N-desisopropylation is mediated mainly by CYP1A2.

    abstract::1. Studies using human liver microsomes and six recombinant human CYP isoforms (i.e. CYP1A2, 2A6, 2B6, 2D6, 2E1 and 3A4) were performed to identify the cytochrome P450 (CYP) isoform(s) involved in the ring 4-hydroxylation and side-chain N-desisopropylation of propranolol enantiomers in humans. 2. alpha-Naphthoflavone ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1995.tb04472.x

    authors: Yoshimoto K,Echizen H,Chiba K,Tani M,Ishizaki T

    更新日期:1995-04-01 00:00:00

  • Antihypertensive effects and pharmacokinetics of single and consecutive doses of cilazapril in hypertensive patients with normal or impaired renal function.

    abstract::1. A 1.25 mg dose of cilazapril, a new angiotensin-converting enzyme (ACE) inhibitor, was administered orally to two groups of hypertensive patients, five with normal renal function (NRF) and seven with impaired renal function (IRF), once daily for 5 or 8 consecutive days. Blood pressure, heart rate and serum ACE acti...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1989.tb03493.x

    authors: Shionoiri H,Gotoh E,Sugimoto K,Takasaki I,Minamisawa K,Ishii M

    更新日期:1989-01-01 00:00:00

  • Daily administration of the TP receptor antagonist terutroban improved endothelial function in high-cardiovascular-risk patients with atherosclerosis.

    abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A(2) and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease. WHAT THIS STUDY ADDS:• ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.2010.03858.x

    authors: Lesault PF,Boyer L,Pelle G,Covali-Noroc A,Rideau D,Akakpo S,Teiger E,Dubois-Randé JL,Adnot S

    更新日期:2011-06-01 00:00:00

  • The effects of advanced age and serum α1 -acid glycoprotein on docetaxel unbound exposure and dose-limiting toxicity in cancer patients.

    abstract:AIM:α1 -Acid glycoprotein (AAG), which is a major binding protein of docetaxel, is considered to be a determinant for docetaxel pharmacokinetics. However, there are no reports about the impact of serum AAG on pharmacokinetics and pharmacodynamics in elderly patients treated with docetaxel. The aim of this prospective s...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.13354

    authors: Kenmotsu H,Imamura CK,Ono A,Omori S,Nakashima K,Wakuda K,Taira T,Naito T,Murakami H,Takahashi T,Tanigawara Y

    更新日期:2017-11-01 00:00:00

  • Jejunal and ileal absorption of oxprenolol in man: influence of nutrients and digestive secretions on jejunal absorption and systemic availability.

    abstract::1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxpre...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1987.tb03178.x

    authors: Godbillon J,Vidon N,Palma R,Pfeiffer A,Franchisseur C,Bovet M,Gosset G,Bernier JJ,Hirtz J

    更新日期:1987-09-01 00:00:00

  • The pre- and post-authorisation data published by the European medicines agency on the use of biologics during pregnancy and lactation.

    abstract:AIMS:The effects of biologics on reproduction/lactation are mostly unknown although many patients that receive biologics are women of reproductive age. The first objective of this study was to investigate the publicly available data on pregnancy/lactation before and after marketing authorization in Europe of biologics ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.14145

    authors: Ghalandari N,Dolhain RJEM,Hazes JMW,Siezen CLE,van der Laan JW,Crijns HJMJ,van Puijenbroek EP,van der Woude CJ

    更新日期:2020-03-01 00:00:00