Trial reportJournal of cardiovascular pharmacology2015
Individual and Combined Associations of Genetic Variants in CYP3A4, CYP3A5, and SLCO1B1 With Simvastatin and Simvastatin Acid Plasma Concentrations.
Trial report in Journal of cardiovascular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Effects ofFrontiers in pharmacology · 2023Pooled it
- Genomewide Association Study of Simvastatin Pharmacokinetics.Clinical pharmacology and therapeutics · 2022Pooled it
- Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.Clinical and translational science · 2017Trial
- Evaluating genotype-treatment interactions for high-risk medications in British general practice: a retrospective cohort study using UK Biobank.The British journal of general practice : the journal of the Royal College of General Practitioners · 2026Article
- Bioequivalence Study of Two Formulations of Simvastatin 20 mg Tablet in Healthy Filipino Participants under Fasting Conditions: A Randomized, Open-label, Two-way Crossover Study.Acta medica Philippina · 2024Article
- Insight into Risk Factors, Pharmacogenetics/Genomics, and Management of Adverse Drug Reactions in Elderly: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The frequency of majorPharmacogenomics · 2023Article
- A Drug-Drug Interaction Study to Evaluate the Impact of Simvastatin and Itraconazole on Erlotinib Pharmacokinetics in Rats by UPLC-MS/MS.Drug design, development and therapy · 2023Article
- Review
- Drug-drug-gene interactions and adverse drug reactions.The pharmacogenomics journal · 2020Review
- Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates.Biomedicines · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Our objective was to evaluate the associations of genetic variants affecting simvastatin (SV) and simvastatin acid (SVA) metabolism [the gene encoding cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)*22 and the gene encoding cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5)*3] and transport [the gene encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1) T521C] with 12-hour plasma SV and SVA concentrations. The variants were genotyped, and the concentrations were quantified by high performance liquid chromatography-tandem mass spectrometry in 646 participants of the Cholesterol and Pharmacogenetics clinical trial of 40 mg/d SV for 6 weeks. The genetic variants were tested for association with 12-hour plasma SV, SVA, or the SVA/SV ratio using general linear models. CYP3A5*3 was not significantly associated with 12-hour plasma SV or SVA concentration. CYP3A4*1/*22 participants had 58% higher 12-hour plasma SV concentration compared with CYP3A4*1/*1 participants (P = 0.006). SLCO1B1 521T/C and 521C/C participants had 71% (P < 0.001) and 248% (P < 0.001) higher 12-hour plasma SVA compared with SLCO1B1 521T/T participants, respectively. CYP3A4 and SLCO1B1 genotypes combined categorized participants into low (<1), intermediate (≈1), and high (>1) SVA/SV ratio groups (P = 0.001). In conclusion, CYP3A4*22 and SLCO1B1 521C were significantly associated with increased 12-hour plasma SV and SVA concentrations, respectively. CYP3A5*3 was not significantly associated with 12-hour plasma SV or SVA concentrations. The combination of CYP3A4*22 and SLCO1B1 521C was significantly associated with SVA/SV ratio, which may translate into different clinical SV risk/benefit profiles.
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What OpenQuestion holds
Registered trials
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.