Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several‐fold in patients with atorvastatin‐induced myopathy

  title={Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several‐fold in patients with atorvastatin‐induced myopathy},
  author={Monica Hermann and Martin Pr{\o}ven Bogsrud and Espen Molden and Anders Nikolai {\AA}sberg and Beata U. Mohebi and Leiv Ose and Kjetil Retterst{\o}l},
  journal={Clinical Pharmacology \& Therapeutics},
Guideline for SLCO 1 B 1 and Simvastatin-Induced Myopathy : 2014 Update
Evidence from the literature supporting a single coding singlenucleotide polymorphism in SLCO1B1 increases systemic exposure to simvastatin and the risk of muscle toxicity and therapeutic recommendations are provided.
Effect of Cytochrome P450 3A5 Genotype on Atorvastatin Pharmacokinetics and Its Interaction with Clarithromycin
To assess the effects of the cytochrome P450 (CYP) 3A genotype, CYP3A5, on atorvastatin pharmacokinetics and its interaction with clarithromycin.
Genetic determinants of statin-associated myopathy.
Genome-wide studies suggest that there is a strong candidate variant within the SLCO1B1 gene (rs4149056) for statin-associated myopathy in a UK (European) population, and an enhanced understanding ofstatin-related myopathy may lead to safer drug development and use.
The potential of Atorvastatin for chronic lung diseases therapy
  • Alaa S. Tulbah
  • Chemistry
    Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society
  • 2020
Atorvastatin Metabolite Measurements as a Diagnostic Tool for Statin-Induced Myopathy
An altered metabolic pattern of atorvastatin in patients with SIM is confirmed and substantiates a central role of the lactone forms of statins in future investigations of statin myotoxicity.
Effects of SLCO1B1 and GATM gene variants on rosuvastatin-induced myopathy are unrelated to high plasma exposure of rosuvastatin and its metabolites
SLCO1B1 and GATM genetic variants are potential biomarkers for predicting RST-induced myopathy, and their effects on SIM are unrelated to the high plasma exposure of RST and its metabolites.
Pharmacogenetics of Statin-Induced Myopathy: A Focused Review of the Clinical Translation of Pharmacokinetic Genetic Variants
As the use of statins is extremely common and SIM continues to occur in a significant number of patients, future research investments in pharmacokinetic genetic variants have the potential to make a profound impact on public health.
Pharmacogenetics of Statin-Induced Myotoxicity
This review provides an update on the genetic risk factors associated with statin-induced myotoxicity (SIM), and indicates that SIM is multifactorial.
Development of a Population Pharmacokinetic Model for Atorvastatin Acid and Its Lactone Metabolite
A population pharmacokinetic model was developed and validated to describe atorvastatin acid and its lactone metabolite concentration-time data and it was demonstrated that the model adequately described the pharmacokinetics of both species.
Atorvastatin Pleiotropism: Role in Cardioprotection
The present review article summarizes about the numerous pleiotropic effects exhibited by atorvastatin in affording cardioprotection.


Effect of itraconazole on the pharmacokinetics of atorvastatin
CYP3A5 Genotype has a Dose‐dependent Effect on ABT‐773 Plasma Levels
β-Oxidation of Simvastatin in Mouse Liver Preparations
The involvement of CoASH and NAD+ and the presence of the four metabolic intermediates suggest that SVA (and presumably the other statins) is a substrate for the β-oxidation enzyme complex in mice.
Statin‐associated myopathy
Myopathy occurs in 0.1%–0.2% of patients receiving statins in clinical trials and is a known complication of statin use.
Effect of Age and Gender on Pharmacokinetics of Atorvastatin in Humans
It is unclear whether these age‐ and gender‐related differences in the pharmacokinetics of atorvastatin will be clinically important, and results of subsequent safety and efficacy trials should help clarify the clinical significance of these pharmacokinetic differences.
Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization.
The active forms of all marketed hydroxymethylglutaryl (HMG)-CoA reductase inhibitors share a common dihydroxy heptanoic or heptenoic acid side chain. In this study, we present evidence for the
Multiple Transporters Affect the Disposition of Atorvastatin and Its Two Active Hydroxy Metabolites: Application of in Vitro and ex Situ Systems
Interaction of ATV with hepatic uptake transporter organic anion transporting polypeptide (Oatp) and efflux transporter multidrug resistance associated protein 2 (MRP2/Mrp2) in vitro and ex situ and inhibition of Oatp-mediated uptake seems to be the major determinant for interaction between ATV and RIF.
Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8.
All the statins tested, except rosuvastatin and pravastatin, had a significant inhibitory effect on the activity of CYP2C8 in vitro.
Frequency of single nucleotide polymorphisms in the P‐glycoprotein drug transporter MDR1 gene in white subjects
P‐glycoprotein, the gene product of MDR1, confers multidrug resistance against antineoplastic agents but also plays an important role in the bioavailability of common drugs in medical treatment.