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Exploratory Research in Clinical and... Mar 2024While statin therapy is the preferred treatment for hyperlipidemia, literature supports the low-density lipoprotein (LDL) lowering effects associated with red yeast...
BACKGROUND
While statin therapy is the preferred treatment for hyperlipidemia, literature supports the low-density lipoprotein (LDL) lowering effects associated with red yeast rice, berberine, and . Dietary supplements may be perceived as a more affordable alternative to prescription medication.
OBJECTIVE
We determined cost-effectiveness of generic pravastatin versus single-ingredient dietary supplements in relation to LDL lowering effect.
METHODS
Data from meta-analyses and systematic reviews was extracted to calculate pooled weighted mean LDL differences amongst generic pravastatin and single ingredient dietary supplements. The effect was then divided by average 30-day costs and compared amongst agents.
RESULTS
The greatest difference was seen in pravastatin 40 mg [MD -57.88 mg/dL (95%CI: - 64.80 to -50.96)], followed by pravastatin 10 mg [MD -41.30 mg/dL (95%CI: 63.30 to - 19.40)], red yeast rice [MD -25.39 (95%CI: -32.98 to -17.81)], berberine [MD -15.13 (95%CI: -21.78 to -8.48)], and [MD -9.51 mg/dL (95%CI: -22.13 to - 0.10)]. were divided by mean difference to calculate cost per mg/dL reduction in LDL. Cost-effectiveness was greatest for pravastatin 10 mg [$0.66/mg/dL LDL reduction (range: $0.39 to $1.13)], followed by pravastatin 40 mg [$0.74/mg/dL LDL reduction (range: $0.66 to $0.84)], berberine [$0.81/mg/dL LDL reduction (range: $0.56 to $1.44)], red yeast rice [$0.84/mg/dL reduction (range: $0.67 to $1.13)], and [$0.88/mg/dL LDL reduction (range: $0.38 to $82.02)].
CONCLUSION
Pravastatin is most cost-effective in each scenario whether or not prescription insurance is utilized.
PubMed: 38486611
DOI: 10.1016/j.rcsop.2024.100428 -
Journal of Pharmaceutical Health Care... Aug 2023Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients...
BACKGROUND
Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients with such a dysfunction, a simple suspension method, in which solid medicines are disintegrated and suspended using warm water, has been developed and widely used in Japanese clinical settings. However, there is little information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. In this study, the chemical stability of typical cholesterol-lowering drugs was investigated in a simple co-suspension with alkaline magnesium oxide (MgO) which is frequently used as a laxative or antacid in Japan.
METHODS
A cholesterol-lowering drug (one tablet) was soaked with or without MgO in warm water (55°C), and the vessel was left at room temperature for 10 min or 5 h. The suspensions prepared were then analyzed by high-performance liquid chromatography. Degradation products were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry for the structural elucidation.
RESULTS
In the simple co-suspension with MgO, no significant degradation was observed for atorvastatin or pravastatin, while a significant decrease of the recovery from the co-suspension was observed for rosuvastatin after 5 h. On the other hand, simvastatin and ezetimibe co-suspended with MgO were partially degraded to simvastatin acid and a pyran compound, respectively.
CONCLUSIONS
A simple co-suspension with MgO is feasible for atorvastatin, pravastatin, and rosuvastatin, although the rosuvastatin tablet should not be left soaking for a long time. Further it is inadvisable to suspend simvastatin or ezetimibe together with MgO because of their partial degradation.
PubMed: 37644559
DOI: 10.1186/s40780-023-00301-1 -
CNS & Neurological Disorders Drug... Oct 2023Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability...
INTRODUCTION
Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death.
METHODS
Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified.
RESULTS
Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects.
CONCLUSION
The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses.
PubMed: 37855296
DOI: 10.2174/0118715273270503230928100141 -
Pharmacological Reports : PR Feb 2024Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced...
BACKGROUND
Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced side effect experienced by many patients. Recently, a combination of bisphosphonates (zoledronic acid) and statins (pravastatin), or ZOPRA, was shown to radio-protect normal tissues by enhancing DNA double-strand breaks (DSB) repair mechanism. However, there are no studies assessing the effect of ZOPRA on cancerous cells. The purpose of this study is to characterize the in vitro effect of the zoledronic acid (ZO), pravastatin (PRA), and ZOPRA treatment on the molecular and cellular radiosensitivity of breast cancer cell lines.
MATERIALS
Two breast cancer cell lines, MDA MB 231 and MCF-7, were tested. Cells were treated with different concentrations of pravastatin (PRA), zoledronate (ZO), as well as their ZOPRA combination, before irradiation. Anti-γH2AX and anti-pATM immunofluorescence were performed to study DNA DSB repair kinetics. MTT assay was performed to assess cell proliferation and viability, and flow cytometry was performed to analyze the effect of the drugs on the cell cycle distribution. The clonogenic assay was used to assess cell survival.
RESULTS
ZO, PRA, and ZOPRA treatments were shown to increase the residual number of γH2AX foci for both cell lines. ZOPRA treatment was also shown to reduce the activity of the ATM kinase in MCF-7. ZOPRA induced a significant decrease in cell survival for both cell lines.
CONCLUSIONS
Our findings show that pretreatment with ZOPRA can decrease the radioresistance of breast cancer cells at the molecular and cellular levels. The fact that ZOPRA was previously shown to radioprotect normal tissues, makes it a good candidate to become a therapeutic window-widening drug.
Topics: Humans; Female; MCF-7 Cells; DNA Repair; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Breast Neoplasms; Diphosphonates; Zoledronic Acid; Pravastatin; Radiation Tolerance; DNA; Cell Line, Tumor
PubMed: 38151641
DOI: 10.1007/s43440-023-00560-7 -
Advances in Therapy Jun 2024Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in...
INTRODUCTION
Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice.
METHODS
This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety.
RESULTS
We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks.
CONCLUSION
Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function.
TRIAL REGISTRATION NUMBER
NCT05107063 submitted October 27, 2021.
PubMed: 38880822
DOI: 10.1007/s12325-024-02862-5 -
CPT: Pharmacometrics & Systems... Jun 2024OATP1B facilitates the uptake of xenobiotics into hepatocytes and is a prominent target for drug-drug interactions (DDIs). Reduced systemic exposure of OATP1B substrates...
OATP1B facilitates the uptake of xenobiotics into hepatocytes and is a prominent target for drug-drug interactions (DDIs). Reduced systemic exposure of OATP1B substrates has been reported following multiple-dose rifampicin; one explanation for this observation is OATP1B induction. Non-uniform hepatic distribution of OATP1B may impact local rifampicin tissue concentrations and rifampicin-mediated protein induction, which may affect the accuracy of transporter- and/or metabolizing enzyme-mediated DDI predictions. We incorporated quantitative zonal OATP1B distribution data from immunofluorescence imaging into a PBPK modeling framework to explore rifampicin interactions with OATP1B and CYP substrates. PBPK models were developed for rifampicin, two OATP1B substrates, pravastatin and repaglinide (also metabolized by CYP2C8/CYP3A4), and the CYP3A probe, midazolam. Simulated hepatic uptake of pravastatin and repaglinide increased from the periportal to the pericentral region (approximately 2.1-fold), consistent with OATP1B distribution data. Simulated rifampicin unbound intracellular concentrations increased in the pericentral region (1.64-fold) compared to simulations with uniformly distributed OATP1B. The absolute average fold error of the rifampicin PBPK model for predicting substrate maximal concentration (C) and area under the plasma concentration-time curve (AUC) ratios was 1.41 and 1.54, respectively (nine studies). In conclusion, hepatic OATP1B distribution has a considerable impact on simulated zonal substrate uptake clearance values and simulated intracellular perpetrator concentrations, which regulate transporter and metabolic DDIs. Additionally, accounting for rifampicin-mediated OATP1B induction in parallel with inhibition improved model predictions. This study provides novel insight into the effect of hepatic OATP1B distribution on site-specific DDI predictions and the impact of accounting for zonal transporter distributions within PBPK models.
PubMed: 38898552
DOI: 10.1002/psp4.13188 -
Hypertension Research : Official... Jul 2024
PubMed: 38750222
DOI: 10.1038/s41440-024-01692-w -
American Journal of Perinatology Feb 2024This study aimed to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing PE and the maternal and perinatal... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study aimed to evaluate the effect of pravastatin to prevent preeclampsia (PE) in pregnant women at a high risk of developing PE and the maternal and perinatal outcomes and the soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PlGF) ratio.
STUDY DESIGN
This is an open-labeled randomized controlled trial (RCT), a part of INOVASIA (Indonesia Pravastatin to Prevent Preeclampsia study) trial. Pregnant women at a high risk of developing PE were recruited and randomized into an intervention group (40) and a control group (40). The inclusion criteria consisted of pregnant women with positive clinical risk factor and abnormal uterine artery Doppler examination at 10 to 20 weeks' gestational age. The control group received low dose aspirin (80 mg/day) and calcium (1 g/day), while the intervention group received additional pravastatin (20-mg twice daily) starting from 14 to 20 weeks' gestation until delivery. Research blood samples were collected before the first dose of pravastatin and before delivery. The main outcome was the rate of maternal PE, maternal-perinatal outcomes, and sFlt-1, PlGF, sFlt-1/PlGF ratio, and soluble endoglin (sEng) levels.
RESULTS
The rate of PE was (nonsignificantly) lower in the pravastatin group compared with the control group (17.5 vs. 35%). The pravastatin group also had a (nonsignificant) lower rate of severe PE, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, acute kidney injury, and severe hypertension. The rate of (iatrogenic) preterm delivery was significantly ( = 0.048) lower in the pravastatin group ( = 4) compared with the controls ( = 12). Neonates in the pravastatin group had significantly higher birth weights (2,931 ± 537 vs. 2,625 ± 872 g; = 0.006), lower Apgar's scores < 7 (2.5 vs. 27.5%, = 0.002), composite neonatal morbidity (0 vs. 20%, = 0.005), and NICU admission rates (0 vs. 15%, = 0.026). All biomarkers show a significant deterioration in the control group compared with nonsignificant changes in the pravastatin group.
CONCLUSION
Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes by improving the angiogenic imbalance.
KEY POINTS
· Prophylactic pravastatin was associated with a significantly lower rate of adverse perinatal outcome.. · The sFlt1/PlGF ratio stabilized in the pravastatin group compared with a deterioration in the control group.. · Pravastatin holds promise in the secondary prevention of PE and placenta-mediated adverse perinatal outcomes..
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pre-Eclampsia; Pravastatin; Pregnancy Proteins; Placenta Growth Factor; Biomarkers; Endoglin; Vascular Endothelial Growth Factor Receptor-1
PubMed: 34666379
DOI: 10.1055/a-1673-5603 -
AAPS PharmSciTech Feb 2024Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate...
Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate transdermal patches containing PVS-loaded nanoemulsions (PVS-NEs) to increase PVS's hypolipidemic and hepatoprotective activities. PVS-NEs were prepared using the aqueous titration method, where oleic acid was chosen as an oil phase, and span 80 and tween 80 were used as surfactant and cosurfactant respectively. Droplet size (DS), polydispersity index (PDI), zeta potential (ZP), clarity, and thermodynamic stability of NEs were all characterized. Also, PVS-NEs (NE2) with 50% oil phase, 40% SC mix 2:1, and 10% water were selected as an optimum formula based on the results of DS (251 ± 16), PDI (0.4 ± 0.16), and ZP (-70 ± 10.4) to be incorporated into a transdermal patch, and PVS-NE2 loaded transdermal patches (PVS-NE2-TDPs) were prepared by solvent evaporation method. F1 patch with HPMC E15 and PVP K30 in a ratio of 3:1 represented satisfactory patch properties with good drug-excipients compatibility. Thus, it was selected as an optimum patch formula. The optimized F1 patch was characterized for thickness, moisture content, weight variation, and drug-excipients incompatibility. Therefore, it was subjected to ex vivo skin permeation and finally pharmacodynamic studies. Ex vivo permeation studies of F1 revealed that the cumulative amount of PVS permeated across rat skin was 271.66 ± 19 µg/cm in 72 h, and the pharmacodynamic studies demonstrated that the F1 patch was more effective in treating hyperlipidemia than PVS-TDP (control patch) based on both blood analysis and histopathological examination. .
Topics: Rats; Animals; Administration, Cutaneous; Pravastatin; Excipients; Transdermal Patch; Hyperlipidemias; Rats, Wistar
PubMed: 38332233
DOI: 10.1208/s12249-024-02746-5 -
American Journal of Obstetrics and... Aug 2023
Topics: Pregnancy; Female; Animals; Humans; Pravastatin; Pre-Eclampsia; Vascular Endothelial Growth Factor Receptor-1; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 36972893
DOI: 10.1016/j.ajog.2023.03.036