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Profiles of Drug Substances,... 2014Pravastatin sodium is an [HMG-CoA] reductase inhibitor and is a lipid-regulating drug. This monograph includes the description of the drug: nomenclature, formulae,... (Review)
Review
Pravastatin sodium is an [HMG-CoA] reductase inhibitor and is a lipid-regulating drug. This monograph includes the description of the drug: nomenclature, formulae, elemental composition, solubility, appearance, and partition coefficient. The uses and the methods that have been reported for the synthesis of this drug are described. The physical methods that were used to characterize the drug are the X-ray powder diffraction pattern, thermal methods, melting point, and differential scanning calorimetry. This chapter also contains the following spectra of the drug: the ultraviolet spectrum, the vibrational spectrum, the nuclear magnetic resonance spectra, and the mass spectrum. The compendial methods of analysis include the British Pharmacopoeia and the United States Pharmacopoeia methods. Other methods of analysis that are included in this profile are spectrophotometric, electrochemical, polarographic, voltammetric and chromatographic, and immunoassay methods. The chapter also contains the pharmacokinetics, metabolism, stability, and articles that reviewed pravastatin sodium manufacturing, characterization, and analysis. One hundred and sixty-two references are listed at the end of this comprehensive profile.
Topics: Animals; Biotransformation; Chemistry, Pharmaceutical; Drug Stability; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Molecular Structure; Pravastatin
PubMed: 24794911
DOI: 10.1016/B978-0-12-800173-8.00008-8 -
DICP : the Annals of Pharmacotherapy Apr 1991The rate-limiting step in cholesterol biosynthesis is controlled by the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Inhibitors of this enzyme lower... (Review)
Review
The rate-limiting step in cholesterol biosynthesis is controlled by the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Inhibitors of this enzyme lower serum cholesterol very efficiently by increasing cellular uptake of cholesterol-rich, low-density lipoproteins. Pravastatin, a derivative of mevastatin and in the same class as lovastatin, lowers total cholesterol concentrations by 20-30 percent in patients with hypercholesterolemia. In patients who also have hypertriglyceridemia, serum triglyceride levels are decreased. Detailed pharmacokinetic data and long-term adverse-effect experience with pravastatin are extremely limited. The issue of tissue-selectivity for pravastatin has given rise to the marketing terminology "second-generation" HMG-CoA reductase inhibitor, but any clinical advantage of pravastatin over other HMG-CoA reductase inhibitors remains to be demonstrated.
Topics: Animals; Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pravastatin
PubMed: 1926908
DOI: 10.1177/106002809102500410 -
Biochemical and Biophysical Research... Jan 2019Pravastatin sodium on triggering receptor expressed on myeloid cell-1 (TREM-1)-mediated inflammation in human peripheral blood mononuclear cells (PBMCs) has been poorly...
Pravastatin sodium on triggering receptor expressed on myeloid cell-1 (TREM-1)-mediated inflammation in human peripheral blood mononuclear cells (PBMCs) has been poorly investigated. In this study, we isolated PBMCs from the peripheral blood samples of patients with chronic obstructive pulmonary disease, treated the cells with pravastatin sodium, and determined a concentration at which more than 90% cells could survive. Then we treated cells with 10 ng/ml of lipopolysaccharide, added with 10, 50, 100 μM of pravastatin sodium combined with or without LR-12, a known TREM-1 inhibitor. The expression of TREM-1 was determined by quantitative RT-PCR. The levels of TREM-1, IL-6, and TNF-α in cell culture supernatant were measured with ELISA. Simultaneously, NF-κB signaling pathway-related protein p-p65 and p-IκBα were detected by Western blot assay. Results demonstrated that pravastatin sodium significantly mitigated lipopolysaccharide-stimulated TREM-1 over-expression at mRNA and protein levels dose-dependently. Elevated IL-6 and TNF-α levels changed synchronously. LR-12 inhibited the TREM-1 over-expression and inflammatory factor production but did not show extra synergistic effect to pravastatin. Lipopolysaccharide induced phospho-p65 and -IκBα over-expression was weakened significantly when cells were treated with pravastatin sodium. In conclusion, pravastatin could inhibit TREM-1-medieted inflammation and NF-κB signaling pathway was involved.
Topics: Cells, Cultured; Cytokines; Humans; Inflammation; Leukocytes, Mononuclear; Lipopolysaccharides; NF-kappa B; Pravastatin; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 30473214
DOI: 10.1016/j.bbrc.2018.11.098 -
Circulation Research Oct 2021[Figure: see text].
[Figure: see text].
Topics: Animals; Antineoplastic Agents; Autophagy; Autophagy-Related Protein 7; Cardiotoxicity; Doxorubicin; Myocarditis; Pravastatin; Spironolactone; Zebrafish; Zebrafish Proteins
PubMed: 34384247
DOI: 10.1161/CIRCRESAHA.121.319104 -
European Heart Journal Jun 2020Lipoprotein(a) [Lp(a)] is elevated in 20-30% of people. This study aimed to assess the effect of statins on Lp(a) levels. (Meta-Analysis)
Meta-Analysis
AIMS
Lipoprotein(a) [Lp(a)] is elevated in 20-30% of people. This study aimed to assess the effect of statins on Lp(a) levels.
METHODS AND RESULTS
This subject-level meta-analysis includes 5256 patients (1371 on placebo and 3885 on statin) from six randomized trials, three statin-vs.-placebo trials, and three statin-vs.-statin trials, with pre- and on-treatment (4-104 weeks) Lp(a) levels. Statins included atorvastatin 10 mg/day and 80 mg/day, pravastatin 40 mg/day, rosuvastatin 40 mg/day, and pitavastatin 2 mg/day. Lipoprotein(a) levels were measured with the same validated assay. The primary analysis of Lp(a) is based on the log-transformed data. In the statin-vs.-placebo pooled analysis, the ratio of geometric means [95% confidence interval (CI)] for statin to placebo is 1.11 (1.07-1.14) (P < 0.0001), with ratio >1 indicating a higher increase in Lp(a) from baseline in statin vs. placebo. The mean percent change from baseline ranged from 8.5% to 19.6% in the statin groups and -0.4% to -2.3% in the placebo groups. In the statin-vs.-statin pooled analysis, the ratio of geometric means (95% CI) for atorvastatin to pravastatin is 1.09 (1.05-1.14) (P < 0.0001). The mean percent change from baseline ranged from 11.6% to 20.4% in the pravastatin group and 18.7% to 24.2% in the atorvastatin group. Incubation of HepG2 hepatocytes with atorvastatin showed an increase in expression of LPA mRNA and apolipoprotein(a) protein.
CONCLUSION
This meta-analysis reveals that statins significantly increase plasma Lp(a) levels. Elevations of Lp(a) post-statin therapy should be studied for effects on residual cardiovascular risk.
Topics: Atorvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein(a); Pravastatin; Randomized Controlled Trials as Topic; Rosuvastatin Calcium
PubMed: 31111151
DOI: 10.1093/eurheartj/ehz310 -
Biochimica Et Biophysica Acta Nov 1993Pravastatin and pravastatin-lactone are not taken up into extrahepatic cells such as fibroblasts, or hepatoma cells such as AS-30D ascites hepatoma cells or FAO cells....
Pravastatin and pravastatin-lactone are not taken up into extrahepatic cells such as fibroblasts, or hepatoma cells such as AS-30D ascites hepatoma cells or FAO cells. In contrast, pravastatin is taken up into isolated rat hepatocytes by a carrier mediated, saturable, temperature-dependent and energy-dependent mechanism. The kinetic parameters for the saturable uptake are Km 27 microM, Vmax 537 pmol/mg per min. The permeability coefficients were determined to be 9.829 x 10(-7) cm/s at 4 degrees C, 1.76 x 10(-6) cm/s at 7 degrees C, 3.85 x 10(-6) cm/s at 17 degrees C and 5.82 x 10(-6) cm/s at 37 degrees C. The activation energy is 60 kJ/mol for 100 microM pravastatin at 37 degrees C. The Q10 values are between 1.7 and 2.8. In the presence of metabolic inhibitors and in the absence of oxygen, transport is inhibited. Uptake of pravastatin is not dependent on an extracellular to intracellular sodium-gradient. Replacement of chloride by sulfate, nitrate, gluconate or thiocyanate significantly inhibits the uptake of pravastatin. Uptake is competitively inhibited by cholate and taurocholate in the presence and absence of sodium. Pravastatin, however, competitively inhibits the uptake of cholate and taurocholate only in the absence of sodium. In addition, pravastatin-lactone enters liver cells via an energy-dependent, carrier-mediated uptake system. For the saturable energy-dependent part of the hepatocellular uptake a Km value of 9 microM and a Vmax value of 621 pmol/mg per min was determined. The permeability coefficient of pravastatin-lactone uptake is calculated to be 5.41 x 10(-6) cm/s at 37 degrees C. The uptake of pravastatin-lactone is competitively-noncompetitively inhibited by pravastatin and by lovastatin and vice versa. These results indicate that the hepatoselectivity of pravastatin is due to its carrier-mediated uptake into rat hepatocytes via a sodium-independent bile acid carrier. Pravastatin-lactone resembles pravastatin-sodium in its hepatoselectivity.
Topics: Animals; Biological Transport; Cells, Cultured; Kinetics; Lactones; Liver; Male; Pravastatin; Rats; Rats, Sprague-Dawley; Rats, Wistar; Tumor Cells, Cultured
PubMed: 8241247
DOI: 10.1016/0005-2736(93)90272-2 -
American Journal of Obstetrics and... Dec 2021Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia.
OBJECTIVE
We previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women. Here, we report a follow-up, randomized trial of 20 mg pravastatin versus placebo among pregnant women with previous preeclampsia who required delivery before 34+6 weeks' gestation with the objective of evaluating the safety and pharmacokinetic parameters of pravastatin.
STUDY DESIGN
This was a pilot, multicenter, blinded, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12+0 and 16+6 weeks of gestation were assigned to receive a daily pravastatin dose of 20 mg or placebo orally until delivery. In addition, steady-state pravastatin pharmacokinetic studies were conducted in the second and third trimesters of pregnancy and at 4 to 6 months postpartum. Primary outcomes included maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included maternal and umbilical cord blood chemistries and maternal and neonatal outcomes, including rates of preeclampsia and preterm delivery, gestational age at delivery, and birthweight.
RESULTS
Of note, 10 women assigned to receive pravastatin and 10 assigned to receive the placebo completed the trial. No significant differences were observed between the 2 groups in the rates of adverse or serious adverse events, congenital anomalies, or maternal and umbilical cord blood chemistries. Headache followed by heartburn and musculoskeletal pain were the most common side effects. We report the pravastatin pharmacokinetic parameters including pravastatin area under the curve (total drug exposure over a dosing interval), apparent oral clearance, half-life, and others during pregnancy and compare it with those values measured during the postpartum period. In the majority of the umbilical cord and maternal samples at the time of delivery, pravastatin concentrations were below the limit of quantification of the assay. The pregnancy and neonatal outcomes were more favorable in the pravastatin group. All newborns passed their brainstem auditory evoked response potential or similar hearing screening tests. The average maximum concentration and area under the curve values were more than 2-fold higher following a daily 20 mg dose compared with a 10 mg daily pravastatin dose, but the apparent oral clearance, half-life, and time to reach maximum concentration were similar, which is consistent with the previously reported linear, dose-independent pharmacokinetics of pravastatin in nonpregnant subjects.
CONCLUSION
This study confirmed the overall safety and favorable pregnancy outcomes for pravastatin in women at high risk for preeclampsia. This favorable risk-benefit analysis justifies a larger clinical trial to evaluate the efficacy of pravastatin for the prevention of preeclampsia. Until then, pravastatin use during pregnancy remains investigational.
Topics: Adult; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pilot Projects; Pravastatin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Prenatal Care; Treatment Outcome; Young Adult
PubMed: 34033812
DOI: 10.1016/j.ajog.2021.05.018 -
Journal of Reproductive Immunology Nov 2017Pre-eclampsia is a disease of pregnancy affecting 5%-8% of all pregnancies and a leading cause of maternal and fetal mortality. Despite improvements in the diagnosis,... (Review)
Review
Pre-eclampsia is a disease of pregnancy affecting 5%-8% of all pregnancies and a leading cause of maternal and fetal mortality. Despite improvements in the diagnosis, there is no effective method for prevention and treatment. While studies in women are of critical importance, investigation of pathological mechanisms in pregnant women is necessarily limited, and the ability to establish cause and effect relationships, difficult. Mouse models have been instrumental in defining pathogenic mechanisms in preeclampsia and in the identification of pravastatin as a potential treatment to prevent pregnancy complications associated with placental dysfunction. Numerous epidemiological studies provided robust evidence demonstrating that pravastatin exposure during pregnancy does not affect fetal development. In addition, pravastatin is hydrophilic and has a limited passage through the placenta, diminishing any safety concerns. Several pilot studies suggest that pravastatin may be a good option to prevent and treat preeclampsia in women. While these studies are promising, the effectiveness of pravastatin to treat preeclampsia needs to be confirmed by randomized clinical trials.
Topics: Animals; Anticholesteremic Agents; Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Fetal Development; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice; Placenta; Pravastatin; Pre-Eclampsia; Pregnancy
PubMed: 29028516
DOI: 10.1016/j.jri.2017.09.009 -
International Journal of Nanomedicine 2023Pravastatin sodium (PVS) is a hypolipidemic drug which suffers from extensive first-pass metabolism and short half-life. Poly(d,l-lactide--glycolide) (PLGA) is...
PURPOSE
Pravastatin sodium (PVS) is a hypolipidemic drug which suffers from extensive first-pass metabolism and short half-life. Poly(d,l-lactide--glycolide) (PLGA) is considered a promising carrier to improve its hypolipidemic and hepatoprotective activities.
METHODS
PVS-loaded PLGA nanoparticles (PVS-PLGA-NPs) were prepared by double emulsion method using a full 3 factorial design. The in vitro release and the physical stability studies of the optimized PVS-PLGA-NPs (F5) were performed. Finally, both hypolipidemic and hepatoprotective activities of the optimized F5 NPs were studied and compared to PVS solution.
RESULTS
All the studied physical parameters of the prepared NPs were found in the accepted range. The particle size (PS) ranged from 90 ± 0.125 nm to 179.33 ± 4.509 nm, the poly dispersity index (PDI) ranged from 0.121 ± 0.018 to 0.158 ± 0.014. The optimized NPs (F5) have the highest entrapment efficiency (EE%) (51.7 ± 5%), reasonable PS (168.4 ± 2.506 nm) as well as reasonable zeta potential (ZP) (-28.3 ± 1.18mv). Solid-state characterization indicated that PVS is well entrapped into NPs. All NPs have distinct spherical shape with smooth surface. The prepared NPs showed a controlled release profile. F5 showed good stability at 4 ± 2°C during the whole storage period of 3 months. In vivo study and histopathological examination indicated that F5 NPs showed significant increase in PVS hypolipidemic as well as hepatoprotective activity compared to PVS solution.
CONCLUSION
The PVS-PLGA-NPs could be considered a promising model to evade the first-pass effect and showed improvement in the hypolipidemic and hepatoprotective activities compared to PVS solution.
Topics: Polylactic Acid-Polyglycolic Acid Copolymer; Lactic Acid; Polyglycolic Acid; Drug Carriers; Pravastatin; Nanoparticles; Particle Size
PubMed: 36816332
DOI: 10.2147/IJN.S394701 -
Expert Opinion on Drug Metabolism &... Jun 2008It is well known that statins lead to a markable reduction in cardiovascular morbidity and mortality. One of the first and best studied statins is pravastatin, which has... (Review)
Review
BACKGROUND
It is well known that statins lead to a markable reduction in cardiovascular morbidity and mortality. One of the first and best studied statins is pravastatin, which has been studied in both primary and secondary prevention trials. With 40 mg pravastatin daily, total cholesterol can be reduced by 25-34% with a very consistent risk reduction of 24% of death from cardiovascular diseases. Side effects are rare and usually consist of myopathy. Following the Adult Treatment Panel III (ATPIII) guidelines on cholesterol management, apart from therapeutic lifestyle changes, in high-risk patients (including patients with diabetes mellitus), cholesterol-lowering therapy should be targeted at a treatment goal of LDL cholesterol<2.5 mmol/l. Statin-lowering therapy should be commenced to adequately lower cardiovascular risk. Therefore, when the expected 25-34% LDL cholesterol lowering would be enough to reach an LDL<2.5 mmol/l, treatment should be started with pravastatin.
METHOD
Trials have shown that treatment with pravastatin is safe in older patients as well as in children with familial hypercholesterolemia.
RESULTS/CONCLUSION
Since obesity seems to become a worldwide problem and given the low costs of generic pravastatin, it may even be cost-effectively used in developing countries.
Topics: Atherosclerosis; Cardiovascular Diseases; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Practice Guidelines as Topic; Pravastatin; Treatment Outcome
PubMed: 18611121
DOI: 10.1517/17425255.4.6.821