simvastatin (simvastatin, Hanmi / simvastatin CR / Simvast CR)

A transcriptomics-based computational drug repurposing pipeline identifies simvastatin and primaquine as therapeutics for endometriosis.

Oskotsky Tomiko T TT, Tang Xinyu X, Arthurs Erin E, Govil Arpita A et al.

Endometriosis has limited treatment options, prompting the search for data-driven therapeutics. We previously used a transcriptomics-based computational drug repositioning pipeline and identified several drug candidates. Fenoprofen, our top in silico candidate, was validated in a rat model of endometriosis-associated pain. Building on this, we evaluated two additional candidates, simvastatin and primaquine. Using the rat model, we conducted behavioral testing, bulk RNA sequencing, and differential expression analysis to assess their therapeutic potential. We also assessed endometriosis diagnosis among patients prescribed simvastatin in electronic medical records across six University of California (UC) healthcare institutions. Overall, simvastatin and primaquine attenuated pain-associated behaviors and reversed endometriosis-related gene expression changes in our animal model. Moreover, simvastatin prescription was associated with a lower observed relative risk of endometriosis in our retrospective multi-center cohort study. These findings highlight their potential as repurposed therapeutics for endometriosis and support the effectiveness of computational drug repositioning in identifying treatment strategies.

Porokeratosis patients with contact dermatitis to simvastatin can be switched to alternative statins.

Tomsitz Dirk D, Oppel Eva M EM

Clinical relevance of pharmacogenomic information for improving prescribing practices in acutely admitted older medical patients.

Christensen Louise Westberg Strejby LWS, Boas Anne Kirstine AK, Clausen Emilie E, Koch Nicoline Elers NE et al.

Safe prescribing and effective medication review during acute hospitalization depends on accurate information about liver and kidney function because these organs are responsible for the elimination of most medications. While estimates for kidney function are widely used, comparable markers of hepatic drug-metabolizing capacity are not routinely available. We evaluated the clinical relevance of pharmacogenomic (PGx) information for key pharmacogenes implicated in medication elimination in older adults presenting to the emergency department. Fourteen pharmacogenes were analysed using the Personal Medicine Profile™ test. GeneYouIn PillCheck™ software performed genotype-to-phenotype translations, identified drug-gene interactions (DGIs) and generated a clinical decision report based on each patient's actual medication use. Among 125 acutely admitted older medical patients (median age 78.3 years; 10 medications; 7 chronic diseases), PGx testing identified 88 DGIs across 63 patients (50.4%). Of these, 46.5% were considered by clinical experts to be clinically relevant for the individual patient, affecting 33 patients (26.4%) in the total study population. Frequently implicated pharmacogenes included CYP2C19 (25.0%), SLCO1B1 (25.0%), CYP2D6 (20.5%), CYP2C9 (14.8%) and OPRM1 (6.8%), and frequently implicated medications included losartan (13.6%), pantoprazole (12.5%), simvastatin (12.5%), atorvastatin (11.4%) and metoprolol (11.4%). With more than one-quarter of acutely admitted older medical patients having one or more clinically relevant DGIs, these findings suggest that PGx information may have meaningful clinical utility for improving prescribing practices in acute care. However, interpretation in this population requires careful consideration of other factors such as nutritional status and inflammation that may modify pharmacogene activity.

Impact of adsorption-based solidification on the pharmaceutical performance and antidyslipidemic efficacy of simvastatin-ezetimibe SNEDDS.

Priani Sani Ega SE, Sopyan Iyan I, Chaerunisaa Anis Yohana AY, Wilar Gofarana G

Simvastatin and ezetimibe are widely used in combination therapy for dyslipidemia; however, their poor aqueous solubility limits oral bioavailability. This study aimed to develop and characterize liquid and solid self-nanoemulsifying drug delivery systems (L-SNEDDS and S-SNEDDS) containing simvastatin and ezetimibe and to evaluate the impact of adsorption-based solidification on their physicochemical characteristics, dissolution behavior, and antidyslipidemic efficacy. An optimized L-SNEDDS composed of Capryol® 90, Cremophor® RH40, and Transcutol® HP was successfully converted into S-SNEDDS by adsorption onto Neusilin® US2. The optimized L-SNEDDS exhibited rapid self-emulsification, high transmittance, and a globule size of 24.47 ± 0.55 nm, whereas S-SNEDDS readily reconstituted into a nanoemulsion with a globule size of 35.51 ± 0.32 nm. Adsorption-based solidification did not alter the chemical integrity of either drug and maintained both drugs predominantly in an amorphous or molecularly dispersed state. S-SNEDDS markedly increased the apparent solubility of both drugs, and both formulations substantially enhanced drug dissolution compared with the drug suspension, although dissolution from S-SNEDDS was slightly lower than that from L-SNEDDS. In a Poloxamer 407-induced dyslipidemia model, both formulations significantly reduced total cholesterol, LDL-C, and triglyceride levels compared with the dyslipidemic control and produced greater lipid-lowering effects than the drug suspension, while no significant differences were observed between L-SNEDDS and S-SNEDDS. These findings suggest that adsorption-based solidification preserved the pharmaceutical and therapeutic performance of the optimized L-SNEDDS while providing the practical advantages of a solid dosage form, supporting S-SNEDDS as a promising oral lipid-based delivery system for simvastatin-ezetimibe combination therapy.