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

@article{Hermann2006ExposureOA,
  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 P. 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},
  year={2006},
  volume={79}
}
The most serious side effect from statin treatment is myopathy, which may proceed to rhabdomyolysis. This is the first study to investigate whether the pharmacokinetics of either atorvastatin or its metabolites, or both, is altered in patients with atorvastatin‐related myopathy compared with healthy controls. 
View on Wiley
ncbi.nlm.nih.gov
127 Citations
Highly Influential Citations
4
Background Citations
49
Methods Citations
3
Results Citations
3

127 Citations

Citation Type

Citation Type

Guideline for SLCO 1 B 1 and Simvastatin-Induced Myopathy : 2014 Update
Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding singlenucleotide polymorphism, rs4149056T>C, in SLCO1B1 increases systemic exposure to… Expand
Effect of Cytochrome P450 3A5 Genotype on Atorvastatin Pharmacokinetics and Its Interaction with Clarithromycin
TLDR
To assess the effects of the cytochrome P450 (CYP) 3A genotype, CYP3A5, on atorvastatin pharmacokinetics and its interaction with clarithromycin. Expand
Genetic determinants of statin-associated myopathy.
TLDR
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. Expand
Atorvastatin Metabolite Measurements as a Diagnostic Tool for Statin-Induced Myopathy
TLDR
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. Expand
The potential of Atorvastatin for chronic lung diseases therapy
  • Alaa S. Tulbah
  • Medicine
  • Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society
  • 2020
TLDR
The advantages and disadvantages of using ATO under conditions associated with those found in the airways are discussed, which could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases. Expand
Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components
TLDR
Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight. Expand
Effects of SLCO1B1 and GATM gene variants on rosuvastatin-induced myopathy are unrelated to high plasma exposure of rosuvastatin and its metabolites
TLDR
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. Expand
Pharmacogenetics of the response to statins
TLDR
The current data suggest that prospective genotyping for certain variants may be of use in tailoring statin therapy to reduce cardiovascular events and to avoid statin-induced adverse effects. Expand
Pharmacogenetics of Statin-Induced Myopathy: A Focused Review of the Clinical Translation of Pharmacokinetic Genetic Variants
TLDR
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. Expand
UGT1A1*28 is Associated with Decreased Systemic Exposure of Atorvastatin Lactone
TLDR
The low-expression UGT1A1*28(TA)7 allele seems to be associated with decreased systemic exposure of the suspected muscle-toxic metabolite atorvastatin lactone. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 34 REFERENCES
OATP‐C(OATP01B1)*15 is associated with statin‐induced myopathy in hypercholesterolemic patients
TLDR
The genetic contribution to the risk of the statin‐induced myopathy is studied by comparing frequencies of mutant alleles of candidate genes in case and control groups. Expand
Effect of itraconazole on the pharmacokinetics of atorvastatin
TLDR
The aim of this study was to characterize the effect of itraconazole on the pharmacokinetics of atorvastatin, a new HMG‐CoA reductase inhibitor that is metabolized at least in part by CYP3A4. Expand
CYP3A5 Genotype has a Dose‐dependent Effect on ABT‐773 Plasma Levels
The metabolizing enzyme cytochrome P450 (CYP) 3A5 is polymorphically expressed as a result of genetic variants that do not encode functional protein. Because of overlapping substrate specificity with… Expand
Substantially elevated levels of atorvastatin and metabolites in cyclosporine‐treated renal transplant recipients
TLDR
The subtantial increase in systemic exposure combined with unalered terminal half-life could indicate an increased bioavailbility of atorvastatin by inhibition of intestinal efflux. Expand
β-Oxidation of Simvastatin in Mouse Liver Preparations
All current 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors [simvastatin (SV), lovastatin (LV), atorvastatin, pravastatin, fluvastatin, and cerivastatin] are believed to undergo an atypical… Expand
Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients.
  • R. Lins, K. Matthys, +4 authors N. Lameire
  • Medicine
  • Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2003
TLDR
While subtle differences may exist in the metabolic processing of atorvastatin in haemodialysis patients, active drug did not accumulate nor did it show enhanced elimination, and levels were comparable to those measured in healthy volunteers, therefore there is no need to adapt atorVastatin dosage in this particular patient population. Expand
Statin‐associated myopathy
TLDR
Myopathy occurs in 0.1%–0.2% of patients receiving statins in clinical trials and is a known complication of statin use. Expand
beta-Oxidation of simvastatin in mouse liver preparations.
TLDR
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 beta-oxidation enzyme complex in mice. Expand
Effect of Age and Gender on Pharmacokinetics of Atorvastatin in Humans
TLDR
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. Expand
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… Expand
...
1
2
3
4
...