ArticlePharmacogenetics and genomics2013
OATP1B1-related drug-drug and drug-gene interactions as potential risk factors for cerivastatin-induced rhabdomyolysis.
Article in Pharmacogenetics and genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- A Phenotyping Tool for Seven Cytochrome P450 Enzymes and Two Transporters: Application to Examine the Effects of Clopidogrel and Gemfibrozil.Clinical pharmacology and therapeutics · 2025Trial
- Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.Clinical pharmacology and therapeutics · 2016Trial
- Risk Assessment for Drug-Induced Hyperbilirubinemia: A Mechanistic Approach.CPT: pharmacometrics & systems pharmacology · 2026Article
- Prevalence of substances with OATP1B1 inhibitory properties in individual case safety reports of suspected statin-associated myopathy - an analysis of Swiss pharmacovigilance data.European journal of clinical pharmacology · 2026Article
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- Utilizing Pharmacogenomic Data for a Safer Use of Statins among the Emirati Population.Current vascular pharmacology · 2024Article
- The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy.Current drug metabolism · 2024Review
- AssessingPharmaceutics · 2023Article
- Rhabdomyolysis or Severe Acute Hepatitis Associated with the Use of Red Yeast Rice Extracts: an Update from the Adverse Event Reporting Systems.Current atherosclerosis reports · 2023Review
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- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
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- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- Evaluation of a Clinically Relevant Drug-Drug Interaction Between Rosuvastatin and Clopidogrel and the Risk of Hepatotoxicity.Frontiers in pharmacology · 2021Article
- A 96-well culture platform enables longitudinal analyses of engineered human skeletal muscle microtissue strength.Scientific reports · 2020Article
- Transport of Bupropion and its Metabolites by the Model CHO and HEK293 Cell Lines.Drug metabolism letters · 2019Article
- Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions.International journal of molecular sciences · 2018Review
- Precision medicine: does ethnicity information complement genotype-based prescribing decisions?Therapeutic advances in drug safety · 2018Review
- Physiologically Based Pharmacokinetic Modeling Suggests Limited Drug-Drug Interaction Between Clopidogrel and Dasabuvir.Clinical pharmacology and therapeutics · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveGenetic variation in drug metabolizing enzymes and membrane transporters as well as concomitant drug therapy can modulate the beneficial and the deleterious effects of drugs. We investigated whether patients exhibiting rhabdomyolysis who were taking cerivastatin possess functional genetic variants in SLCO1B1 and whether they were on concomitant medications that inhibit OATP1B1, resulting in accumulation of cerivastatin.
methodsThis study had three components: (a) resequencing the SLCO1B1 gene in 122 patients who developed rhabdomyolysis while on cerivastatin; (b) functional evaluation of the identified SLCO1B1 nonsynonymous variants and haplotypes in in-vitro HEK293/FRT cells stably transfected with pcDNA5/FRT empty vector, SLCO1B1 reference, variants, and haplotypes; and (c) in-vitro screening of 15 drugs commonly used among the rhabdomyolysis cases for inhibition of OATP1B1-mediated uptake of cerivastatin in HEK293/FRT cells stably transfected with reference SLCO1B1.
resultsThe resequencing of the SLCO1B1 gene identified 54 variants. In-vitro functional analysis of SLCO1B1 nonsynonymous variants and haplotypes showed that the V174A, R57Q, and P155T variants, a novel frameshift insertion, OATP1B1*14 and OATP1B1*15 haplotype were associated with a significant reduction (P<0.001) in cerivastatin uptake (32, 18, 72, 3.4, 2.1 and 5.7% of reference, respectively). Furthermore, clopidogrel and seven other drugs were shown to inhibit OATP1B1-mediated uptake of cerivastatin.
conclusionReduced function of OATP1B1 related to genetic variation and drug-drug interactions likely contributed to cerivastatin-induced rhabdomyolysis. Although cerivastatin is no longer in clinical use, these findings may translate to related statins and other substrates of OATP1B1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.