Purpose: To evaluate the pharmacokinetics of simvastatin at the maximum tolerated dose (MTD) of 7.5 mg/kg, twice daily, in the context of a pilot trial enrolling patients with recurrent and refractory chronic lymphocytic leukemia.
Methods: Patients received simvastatin orally at MTD for 7 days during a 21-day cycle for 6 cycles. Blood samples were collected during cycle 1. Simvastatin lactone and carboxylate concentrations were measured in plasma and peripheral blood mononuclear cells (PBMCs) using a validated HPLC-MS/MS assay.
Results: Patients accrued to this study showed high variability in their exposure to simvastatin. Exposure was dose proportional (AUC and C max) as compared to those receiving standard hyperlipidemia therapy. Peak plasma concentrations ranged from 0.08 to 2.2 and from 0.03 to 0.6 μM for simvastatin lactone and carboxylate, respectively.
Conclusion: Our study shows that when simvastatin is administered at its MTD, only low micro-molar concentrations are achieved in plasma and PBMCs, which is consistent with the results observed in previous studies with lovastatin, but far lower than the concentrations required for anticancer effects in vitro. However, whether simvastatin at its MTD can confer therapeutic benefits to patients still remains to be determined.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00280-013-2326-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Subgingival Delivery of Statins as an Adjunct in the Non-Surgical Treatment of Periodontitis: A Systematic Review.
Biomedicines
January 2025
Department of Periodontal Diseases and Oral Mucosa Diseases, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Pl. Traugutta 2, 41-800 Zabrze, Poland.
Background/objectives: The gold standard in the non-surgical treatment of periodontitis is scaling and root planning (SRP). In recent years, studies have emerged suggesting additional clinical benefits from the use of statins as an adjunct to classical periodontal disease treatment. The aim of the present study was to review the relevant literature relating to the subgingival use of statins as an adjunctive treatment to the classical, non-surgical treatment of periodontitis, with a particular focus on groups with general factors that may affect the outcome of treatment.
View Article and Find Full Text PDFSimvastatin-Induced Ferroptosis in Orbital Fibroblasts in Graves' Ophthalmopathy.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Purpose: Graves' ophthalmopathy (GO), the most common extrathyroidal manifestation of Graves' disease, is disabling and disfiguring. Recent studies have shown that statins have a protective effect on individuals with GO. Statins were reported to trigger ferroptosis in some disorders, but little is known about whether statins protect against GO via ferroptosis.
View Article and Find Full Text PDFExploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing.
Front Immunol
January 2025
Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Background: SLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.
View Article and Find Full Text PDFHepatotoxicity of statins: a real-world study based on the US Food and Drug Administration Adverse Event Reporting System database.
Front Pharmacol
January 2025
Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Background: Statins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.
View Article and Find Full Text PDFA network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.
NPJ Parkinsons Dis
January 2025
Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!