ArticleActa pharmacologica Sinica2014
Decreased exposure of simvastatin and simvastatin acid in a rat model of type 2 diabetes.
Article in Acta pharmacologica Sinica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models.Molecular cancer therapeutics · 2024Article
- Synergistic Anti-Tumor Effect of Simvastatin Combined to Chemotherapy in Osteosarcoma.Cancers · 2021Article
- Effect of Disease State on the Pharmacokinetics of Bedaquiline in Renal-Impaired and Diabetic Rats.ACS omega · 2021Article
- Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus.BioMed research international · 2021Review
- Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance.Pharmaceutics · 2020Review
- Current trends in drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2019Review
- Characteristics of β-oxidative and reductive metabolism on the acyl side chain of cinnamic acid and its analogues in rats.Acta pharmacologica Sinica · 2019Article
- Simvastatin improves olanzapine-induced dyslipidemia in rats through inhibiting hepatic mTOR signaling pathway.Acta pharmacologica Sinica · 2019Article
- Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy.Scientific reports · 2018Article
- The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1.Scientific reports · 2016Article
- Altered Expression of Transporters, its Potential Mechanisms and Influences in the Liver of Rodent Models Associated with Diabetes Mellitus and Obesity.European journal of drug metabolism and pharmacokinetics · 2016Review
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Authors and funding
12 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
aimSimvastatin is frequently administered to diabetic patients with hypercholesterolemia. The aim of the study was to investigate the pharmacokinetics of simvastatin and its hydrolysate simvastatin acid in a rat model of type 2 diabetes.
methodsDiabetes was induced in 4-week-old rats by a treatment of high-fat diet combined with streptozotocin. After the rats received a single dose of simvastatin (20 mg/kg, po, or 2 mg/kg, iv), the plasma concentrations of simvastatin and simvastatin acid were determined. Simvastatin metabolism and cytochrome P4503A (Cyp3a) activity were assessed in hepatic microsomes, and its uptake was studied in freshly isolated hepatocytes. The expression of Cyp3a1, organic anion transporting polypeptide 2 (Oatp2), multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp) in livers was measured using qRT-PCR.
resultsAfter oral or intravenous administration, the plasma concentrations and areas under concentrations of simvastatin and simvastatin acid were markedly decreased in diabetic rats. Both simvastatin metabolism and Cyp3a activity were markedly increased in hepatocytes of diabetic rats, accompanied by increased expression of hepatic Cyp3a1 mRNA. Furthermore, the uptake of simvastatin by hepatocytes of diabetic rats was markedly increased, which was associated with increased expression of the influx transporter Oatp2, and decreased expression of the efflux transporters Mrp2 and Bcrp.
conclusionDiabetes enhances the metabolism of simvastatin and simvastatin acid in rats via up-regulating hepatic Cyp3a activity and expression and increasing hepatic uptake.
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