A brief review paper of the efficacy and safety of atorvastatin in early clinical trials

Bakker-Arkema, Rebecca; Best, James D.; Fayyad, Rana; Heinonen, Therèse; Marais, A. David; Nawrocki, J.W.; Black, Donald M.

doi:10.1016/s0021-9150(97)06066-8

Cited by 41 publications

(23 citation statements)

References 26 publications

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“…Our findings are consistent with those previously reported by others. 15,21,27,[32][33][34] Equally, atorvastatin therapy induced significant modulation of both the quantitative and qualitative features of plasma lipoprotein subspecies. Total triglyceride-rich lipoproteins and LDL levels were significantly reduced (Ϫ30% and Ϫ28%, respectively) on drug administration.…”

Section: Discussionmentioning

confidence: 99%

Action of Atorvastatin in Combined Hyperlipidemia

Guérin

Lassel

Goff

et al. 2000

ATVB

206

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Abstract-Combined hyperlipidemia (CHL) is characterized by a concomitant elevation of plasma levels of triglyceriderich, very low density lipoproteins (VLDLs) and cholesterol-rich, low density lipoproteins (LDLs). The predominance of small, dense LDLs contributes significantly to the premature development of coronary artery disease in patients with this atherogenic dyslipoproteinemia. In the present study, we evaluated the impact of atorvastatin, a newly developed inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, on the cholesteryl ester transfer protein (CETP)-mediated remodeling of apolipoprotein (apo) B-containing lipoprotein subspecies, and more specifically, the particle subpopulations of VLDL and LDL in CHL. , and dense (Ϫ32%, PϽ0.0008) LDL; moreover, in terms of absolute lipoprotein mass, the reduction in dense LDL levels (mean Ϫ62 mg/dL) was preponderant. In addition, the reduction in plasma dense LDL concentration after therapy was significantly correlated with a reduction in plasma VLDL1 levels (rϭ0.429, Pϭ0.0218). Atorvastatin induced a significant reduction (Ϫ7%, Pϭ0.0039) in total CETP-dependent CET activity, which accurately reflects a reduction in plasma CETP mass concentration. Total CETP-mediated CET from high density lipoproteins to apo B-containing lipoproteins was significantly reduced (Ϫ26%, PϽ0.0001) with drug therapy. Furthermore, CETP activity was significantly correlated with the atorvastatininduced reduction in plasma VLDL1 levels (rϭ0.456, Pϭ0.0138). Indeed, atorvastatin significantly and preferentially decreased CET from HDL to the VLDL1 subfraction (Ϫ37%, Pϭ0.0064), thereby reducing both the levels (Ϫ37%, Pϭ0.0001) and the CE content (Ϫ20%, PϽ0.005) of VLDL1. We interpret our data to indicate that 2 independent but complementary mechanisms may be operative in the atorvastatin-induced reduction of atherogenic LDL levels in CHL: first, a significant degree of normalization of both the circulating levels and the quality of their key precursors, ie, VLDL1, and second, enhanced catabolism of the major LDL particle subclasses ( Key Words: cholesteryl ester transfer protein activity Ⅲ HMGCoA reductase inhibitors Ⅲ lipoprotein subspecies C oncomitant elevation of circulating levels of triglyceride-rich VLDL and cholesterol-rich LDL is recognized as being associated with an increased risk of premature coronary artery disease 1 and is characteristic of subjects who exhibit a lipid phenotype typical of combined hyperlipidemia (CHL). 2 An elevated plasma triglyceride concentration has long been linked to the prevalence of small, dense LDL particles. 3 Moreover, a predominance of small, dense LDL in patients with a combined form of hyperlipidemia contributes significantly to the premature vascular disease characteristic of this atherogenic dyslipoproteinemia. 4,5 It is now established that the plasma triglyceride level in the fasting state constitutes a key determinant of the LDL subfraction profile 3 ; indeed, plasma LDLs are derived principally from the intravascular lipoly...

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Section: Discussionmentioning

confidence: 99%

Action of Atorvastatin in Combined Hyperlipidemia

Guérin

Lassel

Goff

et al. 2000

ATVB

206

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“…Atorvastatin belongs to the class of HMG-CoA reductase inhibitors (statins) and is currently one of the most commonly used medications to treat lipid disorders and prevent cardiovascular events in high-risk individuals [1][2][3]. Similarly to other statins, atorvastatin has been associated with the development of skeletal muscle toxicity (myopathy).…”

Section: Introductionmentioning

confidence: 99%

Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population

Tsamandouras

Guo

Wendling

et al. 2017

Pharmacogenetics and Genomics

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Aim(s): Ethnicity has a modulating role in atorvastatin pharmacokinetics, with Asian subjects reported to have higher exposure compared to Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin pharmacokinetic data and models across ethnic groups. This work aims to develop a population pharmacokinetic model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently it is aimed to identify genetic polymorphisms affecting atorvastatin pharmacokinetics in this population. Methods:Atorvastatin acid and o-OH-atorvastatin acid plasma concentrations, clinical/ demographic characteristics and genotypes for 18 genetic polymorphisms (3, 3, 1, 1, 7, 2 and 1 in the ABCB1, ABCG2, CYP3A4, CYP3A5, SLCO1B1, SLCO2B1 and PPARA genes respectively) were collected from 27 Japanese individuals (taking 10mg atorvastatin once daily) and analysed using a population pharmacokinetics modelling approach. Results:The developed population pharmacokinetic model (one-compartment for atorvastatin acid linked through metabolite formation to an additional compartment describing the disposition of o-OH-atorvastatin acid) accurately described the observed data and the associated population variability. Our analysis suggested that subjects carrying one variant allele for the rs2622604 polymorphism (ABCG2) exhibit a 55% (95%CI: 16%-131%) increase in atorvastatin oral bioavailability relatively to the value in individuals without the variant allele. Conclusion:The current work reports the identification in the Japanese population of a BCRP polymorphism, not previously associated with the pharmacokinetics of any statin, that substantially increases atorvastatin acid and o-OH-atorvastatin acid exposure. The developed model may be of clinical importance in order to guide dosing recommendations tailored specifically for the Japanese.

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“…3 According to IMS Health, Lipitor, the pioneer brand of atorvastatin is the world's one of the biggest selling prescription medicines with cumulative sales in excess of $130 billion, but most of the principal brands are now prescribed worldwide as far cheaper generic medicines. In Bangladesh, about 50 atorvastatin brands with different strengths and dosage forms are available and their average sales volume is nearly 1.17 crore taka monthly in the national local market according to Bangladesh Directorate General of Drug Administration (DGDA).…”

Section: Introductionmentioning

confidence: 99%

Bioequivalence Studies and Pharmacokinetic Properties of Atorvastatin 40Mg Tablet in Healthy Bengali Subjects

Saha

Khan

Poddar

et al. 2017

MOJBB

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Abbreviations: t max , time to reach the maximum concentration; C max , maximum plasma concentration; t 1/2 , half-life; AUC 0-24 , area under the plasma time curve up to last quantifiable time; AUC 0-∞ , area under the plasma time curve up to time infinity; k el , elimination rate constant; NCDs, non-communicable diseases; DGDA, directorate general of drug administration; TPR, total peripheral resistance IntroductionThere is an emerging importance of bioequivalence and pharmacokinetics analysis of highly prescribed brand drugs to judge their therapeutic effectiveness, toxicity, and quality to ensure therapeutic validity and patient's safety. Statin classes of lipidlowering agents are most commonly used treatment intervention for Non-Communicable Diseases (NCDs) like diabetes, obesity, hypertension, and dyslipidemia.1 Atorvastatin is an FDA approved synthetic lipid reducing agent under statin class. This drug, also known as 2-(4-fluorophenyl) -βR, δR-dihydroxy-5-(1-methyl ethyl)-3-phenyl-4(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid (Figure 1), is a second generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor.2 This synthetic HMG-CoA reductase inhibitor significantly lowers total cholesterol, low-density lipoprotein cholesterol, and plasma triglycerides in clinical studies.3 According to IMS Health, Lipitor, the pioneer brand of atorvastatin is the world's one of the biggest selling prescription medicines with cumulative sales in excess of $130 billion, but most of the principal brands are now prescribed worldwide as far cheaper generic medicines. In Bangladesh, about 50 atorvastatin brands with different strengths and dosage forms are available and their average sales volume is nearly 1.17 crore taka monthly in the national local market according to Bangladesh Directorate General of Drug Administration (DGDA). This indicates widespread prescribing of this cholesterol-lowering drug in Bangladesh. However, there is no bioequivalence data for any of existing 50 brands of atorvastatin. Dose-dependent lowering of total cholesterol, LDL cholesterol and triglyceride levels have been noticed after oral administration of atorvastatin to patients with hypercholesterolemia and to patients who have hypertriglyceridemia. 4,5 The usual starting dose is 10mg atorvastatin daily. The dose should be adjusted in accordance with plasma lipid levels and can be increased to up to 80mg daily. AbstractThe present study is aimed to investigate the single-dosing pharmacokinetics of two pharmaceutical formulations of atorvastatin 40mg tablet, test (T) sample (Stacor®) and reference (R) sample (Lipitor®) in Bengali subjects. An open-label, randomizedsequence, two-way, two-period crossover study was designed with 24 healthy Bengali male volunteers. Plasma samples collected before and over 0.5-72.0h after a single oral dose per subject. Samples were analyzed by solid phase extraction method and a validated LCMS/MS method. The non-compartmental pharmacokinetic model was used to measure pharmacokinetic parameters of peak plas...

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A brief review paper of the efficacy and safety of atorvastatin in early clinical trials

Cited by 41 publications

References 26 publications

Action of Atorvastatin in Combined Hyperlipidemia

Action of Atorvastatin in Combined Hyperlipidemia

Modelling of atorvastatin pharmacokinetics and the identification of the effect of a BCRP polymorphism in the Japanese population

Bioequivalence Studies and Pharmacokinetic Properties of Atorvastatin 40Mg Tablet in Healthy Bengali Subjects

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