HMG-CoA reductase [IC50 = 5.6 μM.]

Pravastatin (CS-514), a statin medicine, is used in combination with diet, exercise, and weight loss to decrease cholesterol and prevent cardiovascular disease[1].
Pravastatin Sodium is the sodium salt of pravastatin with cholesterol-lowering and potential antineoplastic activities. Pravastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses by suppressing MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. In addition, pravastatin, like other statins, exhibits pro-apoptotic, growth inhibitory, and pro-differentiation activities in a variety of tumor cells; these antineoplastic activities may be due, in part, to inhibition of the isoprenylation of Ras and Rho GTPases and related signaling cascades.

Pravastatin (40 mg, single dose) causes a reduction in cholesterol synthesis in human monocyte derived macrophages by 62% in healthy subjects and 47% in hypercholesterolaemic patients. Pravastatin (40 mg/day, 8 weeks) results in a 55% inhibition of cholesterol synthesis and a 57% increase in LDL degradation in hypercholesterolaemic patients. Pravastatin (30 mg/kg/d) results in decreased length of the dystrophic lesions by 34% and recovery of muscular structure in Male Wistar rats receiving irradiation, associated with decreased CCN2 level.

Determination of Lipid Peroxide Levels in Plasma[2] Products of lipid peroxidation were assessed by the thiobarbituric acid (TBA) reactive substances (TBARS) method, which detects the levels of malondialdehyde (MDA), the main product of lipid peroxidation. Briefly, 100 µL of plasma was added into testing tubes and incubated with 100 µL of distilled water, 50 µL of 8.1% sodium dodecyl sulfate (SDS), 375 µL of acetic acid 20%, and 375 µL of TBA 0.8% for one hour in a water-bath at 95 °C. Then, the samples were centrifuged at 4000 rpm for 10 min. TBA was added to samples and a colorimetric reaction immediately obtained, which was measured through a wavelength of 532 nm, as previously described. The plasmatic levels of MDA were presented in nmol/mL.

Vascular Reactivity[2] Abdominal aorta segments were dissected and cut into four rings (3 mm), in which two rings had their endothelium mechanically removed and two had their endothelium preserved. Each aortic ring was hung between two wire hooks, and placed into an organ chamber containing Krebs–Henseleit solution (NaCl 130; KCl 4.7; CaCl2 1.6; KH2PO4 1.2; MgSO4 1.2; NaHCO3 15; glucose 11.1; in mmol/L) kept at pH 7.4 and 37 °C, and bubbled with 95% O2 and 5% CO2, and then were stabilized under basal tension of 1.5 g.[2]

Female Wistar rats were were allocated in cages with a 12 h light/dark cycle and controlled temperature (23 ± 2 °C), with access to food and water ad libitum. For mating overnight, the animals were kept in cages in the ratio of two females to one male in late afternoon. The following day, the detection of sperm and estrus cells in a vaginal smear confirmed the first day of gestation, and pregnant rats were distributed into four experimental groups:[2]
1. Normotensive Pregnant rats (Norm-Preg group): saline (0.9% NaCl) solution (0.3–0.45 mL) was intraperitoneally (i.p.) administered on days 1, 7, and 14, and saline was administered by gavage from pregnancy day 10 until 19 (n = 8).[2]
2. Normotensive pregnant rats treated with pravastatin (Norm-Preg + Prava group): saline was i.p. administered on days 1, 7, and 14, and pravastatin (10 mg/kg/day) was administrated by gavage from pregnancy day 10 until 19 (n = 8).[2]
3. Hypertensive pregnant rats (HTN-Preg group): hypertension was induced by i.p. administration of 12.5 mg of DOCA on the first day of pregnancy, followed by i.p. injection of 6.5 mg of DOCA on days 7 and 14 of pregnancy; drinking water was replaced by saline from pregnancy day 1 until 19; and saline was administered by gavage from pregnancy day 10 until 19 (n = 8).[2]
4. Hypertensive pregnant rats treated with pravastatin (HTN-Preg + Prava group): hypertension was induced by i.p. administration of 12.5 mg of DOCA on the first day of pregnancy, followed by i.p. injection of 6.5 mg of DOCA on days 7 and 14 of pregnancy; drinking water was replaced by saline from pregnancy day 1 until 19; and pravastatin (10 mg/kg/day) was administrated by gavage from pregnancy day 10 until 19 (n = 8).[2]
On pregnancy day 19, rats were euthanized by overdose of isoflurane followed by exsanguination. Subsequently, a laparotomy was performed for the exposure/removal of the pregnant uterus, and the abdominal aorta was withdrawn. The abdominal aorta was prepared for vascular reactivity experiments. Placental weight and litter size (total number of pups) were recorded. Placenta and plasma were stored at −80 °C until use for biochemical analysis.[2]

Dissolved in water; 30 mg/kg/day; oral administration

Male Wistar rats receiving irradiation for 5 weeks

Absorption, Distribution and Excretion
Pravastatin is absorbed within 60-90 minutes after oral administration, with a bioavailability of only 17%. Pravastatin's polarity results in a high first-pass metabolic rate and incomplete absorption, leading to low bioavailability. Pravastatin is rapidly absorbed from the upper small intestine via proton-coupled carrier-mediated transport, followed by uptake in the liver via sodium-independent bile acid transporters. Peak serum concentrations of pravastatin have been reported to be reached in 1-1.5 hours within the range of 30-55 mcg/L, with an AUC range of 60-90 mcg·h/L. Approximately 70% of the administered pravastatin dose is excreted in feces, and approximately 20% in urine. When pravastatin is administered intravenously, approximately 47% of the administered dose is excreted in urine, and 53% is excreted via bile biotransformation. The reported steady-state volume of distribution for pravastatin is 0.5 L/kg. The pharmacokinetic parameters for this drug in children range from 31 to 37 ml/kg. Clearance of pravastatin in adults is reported to be 6.3–13.5 ml·min/kg, while in children it is 4–11 L/min. In lactating rats, the concentration of pravastatin in breast milk is 7 times higher than in maternal plasma, equivalent to twice the maximum recommended daily dose (MRHD) of 80 mg based on body surface area (mg/m²). In pregnant rats, pravastatin crosses the placenta, and after a single oral dose of 20 mg/day on day 18 of gestation, the concentration in fetal tissue reaches 30% of the maternal plasma concentration, equivalent to twice the maximum recommended daily dose (MRHD) of 80 mg based on body surface area (mg/m²). Low radioactivity: This substance was found in rat fetuses orally administered radiolabeled pravastatin sodium.
Dogs are unique in that they have significantly higher systemic exposure to pravastatin compared to all other tested species, including humans. A pharmacokinetic study in dogs showed that at a dose of 1.1 mg/kg (equivalent to a 40 mg dose in humans), pravastatin was eliminated more slowly in dogs than in humans. The absolute bioavailability in dogs was twice that in humans, with estimated renal and hepatic extracts of pravastatin estimated to be approximately one-tenth and one-half of those in humans, respectively. When comparing pravastatin concentrations in plasma or serum of rats, dogs, rabbits, monkeys, and humans, based on CMAX and AUC, the exposure in dogs was significantly higher than in other species. In humans, the mean AUC at a therapeutic dose of 40 mg was approximately 100 times lower than the mean AUC at an ineffective dose of 12.5 mg/kg in dogs, and approximately 180 times lower than the mean AUC at a hemorrhage threshold dose of 25 mg/kg in dogs. For more complete data on the absorption, distribution, and excretion of pravastatin (23 items in total), please visit the HSDB records page.

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Metabolism/Metabolites
Pivastatin undergoes extensive first-pass metabolism in the liver after initial administration. However, pravastatin metabolism is not significantly affected by cytochrome P-450 isoenzyme activity, resulting in low levels of metabolism in the liver. Consequently, the drug is highly exposed in peripheral tissues. Pravastatin metabolism is primarily controlled by glucuronidation, with minimal involvement of CYP3A enzymes. No active metabolites are produced after metabolism. Metabolism primarily occurs in the stomach, with minor processing by the kidneys and liver. The major metabolite of pravastatin is the 3α-hydroxy isomer. The activity of this metabolite is clinically negligible. The main biotransformation pathways of pravastatin include: (a) isomerization to 6-epipravastatin and the 3α-hydroxy isomer of pravastatin (SQ 31,906); and (b) enzymatic cyclic hydroxylation to SQ 31,945. The HMG-CoA reductase inhibitory activity of the 3α-hydroxy isomer metabolite (SQ 31,906) is approximately 1/10 to 1/40 that of the parent compound. Pravastatin undergoes extensive first-pass metabolism in the liver (extraction rate 0.66).

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Biological half-life
The elimination half-life of pravastatin has been reported to be 1.8 hours.
Following a single oral dose of (14)C-pravastatin, the radioactive elimination half-life of pravastatin in humans is 1.8 hours.
In a two-way crossover study, eight healthy male subjects received intravenous and oral (14)C-pravastatin sodium, respectively. ...The estimated mean plasma elimination half-life of pravastatin is 0.8 hours for intravenous administration and 1.8 hours for oral administration. ...

Toxicity Summary
Identification and Uses: Pravastatin is an HMG-CoA reductase inhibitor (i.e., a statin) and belongs to the lipid-lowering drug class. Pravastatin is an odorless white to off-white fine powder or crystalline powder, formulated as tablets. It is used in conjunction with lifestyle interventions to prevent cardiovascular events and treat dyslipidemia. Human Exposure and Toxicity: Pravastatin is contraindicated in pregnant women due to the potential for fetal harm. Rare fatal and non-fatal cases of hepatic failure have been reported in patients taking statins (including pravastatin). Additionally, rare cases of rhabdomyolysis with myoglobinuria leading to acute renal failure have been reported in patients taking pravastatin and other similar drugs. A history of renal impairment may be a risk factor for rhabdomyolysis. Animal Studies: Acute toxicity studies have been conducted in mice and rats. Toxicity symptoms in mice included decreased activity, irregular breathing, ptosis, lacrimation, loose stools, diarrhea, abdominal urine stains, ataxia, crawling behavior, loss of righting reflex, hypothermia, urinary incontinence, piloerection spasms, and/or collapse. Toxicity symptoms in rats included loose stools, diarrhea, decreased activity, irregular breathing, waddling gait, ataxia, loss of righting reflex, and/or weight loss. In a two-year study, administration of pravastatin at doses of 10, 30, or 100 mg/kg body weight showed an increased incidence of hepatocellular carcinoma in male rats at the highest dose. Similarly, a two-year mouse study showed increased incidence of hepatocellular carcinoma in both male and female mice after administration of pravastatin at doses of 250 and 500 mg/kg/day; the incidence of lung adenomas was also increased in female mice. In dogs, high doses of pravastatin sodium are toxic, causing cerebral hemorrhage and clinical manifestations of acute central nervous system toxicity, such as ataxia and seizures. The threshold dose for central nervous system toxicity is 25 mg/kg. No cerebral hemorrhage was observed in any other experimental animals; therefore, the central nervous system toxicity in dogs may be a species-specific effect. During days 7 to 17 of gestation (organogenesis), pregnant rats were administered doses of 4, 20, 100, 500, and 1000 mg/kg/day by gavage. At doses ≥100 mg/kg/day, offspring mortality was increased, and the incidence of cervical and rib deformities was elevated. During days 17 of gestation to day 21 of lactation (weaning), pregnant rats were administered doses of 10, 100, and 1000 mg/kg/day by gavage. At doses ≥100 mg/kg/day, offspring mortality was increased, and developmental delays were observed. In a fertility study of adult rats, pravastatin at daily doses up to 500 mg/kg did not have any adverse effects on fertility or general reproductive function. No evidence of mutagenicity was observed in the following in vitro studies, with or without metabolic activation: microbial mutagenesis using mutant strains of Salmonella Typhimurium or Escherichia coli; positive mutation assays using L5178Y TK +/- mouse lymphoma cells; chromosomal aberration assays using hamster cells; and gene conversion assays using Saccharomyces cerevisiae. Furthermore, no evidence of mutagenicity was found in mouse dominant lethal assays and mouse micronucleus assays.

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Hepatotoxicity
Pivastatin treatment is associated with mild, asymptomatic, and usually transient elevations in serum transaminases. In a pooled analysis of large-scale prospective surveillance studies, ALT levels were elevated in 3% to 7% of patients; however, the incidence of serum enzyme levels exceeding three times the upper limit of normal (ULN) was less than 1.2% in both the pravastatin and placebo groups. Most of these elevations are self-limiting and do not require dose adjustment. Pravastatin rarely causes clinically significant liver injury with symptoms or jaundice, with an estimated incidence of 1 in 100,000 users or less. In case reports, the incubation period ranged from 2 to 9 months, and the pattern of serum enzyme elevation ranged from cholestatic to hepatocellular. Patients usually recovered completely within a few months. Rash, fever, eosinophilia, and autoantibodies were uncommon, but related case reports were few, and the complete clinical syndrome was not clearly defined. Pravastatin appears to be less likely to cause clinically significant liver injury compared to atorvastatin, simvastatin, and rosuvastatin. Probability score: B (likely to cause clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Pravastatin has low concentrations in breast milk, but there is currently no published information on its use during lactation. It is generally believed that women taking statins should not breastfeed due to concerns about disrupting the infant's lipid metabolism. However, some argue that children with homozygous familial hypercholesterolemia receiving statin therapy from age 1 have lower oral bioavailability and pose less risk to breastfed infants, especially pravastatin and rosuvastatin. Until more data are available, particularly in breastfed newborns or preterm infants, alternative medications may be preferred.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein binding
Due to its polarity, pravastatin binds very little to plasma proteins, with the bound form accounting for only about 43-48% of the administered dose. However, the activity of P-glycoprotein and OATP1B1 in luminal apical cells significantly affects the distribution and elimination of pravastatin.

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Interactions
HMG-CoA reductase inhibitors are a class of drugs known as statins. These drugs are highly effective and widely used to treat hypercholesterolemia and prevent morbidity and mortality from cardiovascular disease. Currently, there are seven statins available on the market: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Although these drugs are generally well-tolerated, skeletal muscle abnormalities ranging from myalgia to severe and fatal rhabdomyolysis can still occur. Factors that can increase statin concentrations, such as drug interactions, can increase the risk of these adverse events. Drug interactions depend on the pharmacokinetic characteristics of statins: simvastatin, lovastatin, and atorvastatin are metabolized via cytochrome P450 (CYP) 3A, while the metabolism of other statins is independent of this CYP enzyme. All statins are substrates of the organic anion transporter polypeptide 1B1, an uptake transporter expressed on the hepatocyte membrane, which may also explain some drug interactions. Many HIV-infected individuals have dyslipidemia and comorbidities, which may require statin therapy. HIV protease inhibitors (HIV PIs) are part of recommended antiretroviral therapy regimens and are usually used in combination with two reverse transcriptase inhibitors. Except for nelfinavir, all HIV PIs require combination with a low-dose ritonavir (a potent CYP3A inhibitor) to improve their pharmacokinetic properties. Cobicistat is a novel, potent CYP3A inhibitor currently used in combination with avigravir and will be used in combination with HIV PIs in the future. HCV PIs bocepivir and terabhivir are both CYP3A inhibitors, but with different degrees of inhibition. This article reviews the pharmacokinetic properties of statins and PIs, focusing on their metabolic pathways and explaining clinically significant drug interactions. Simvastatin and lovastatin are metabolized by CYP3A and have the strongest potential to interact with potent CYP3A inhibitors (such as ritonavir or cobistat-enhanced HIV protease inhibitors or hepatitis C virus (HCV) protease inhibitors terabitvir or bosepitvir), therefore concomitant use is contraindicated. Atorvastatin is also a CYP3A substrate, but its interactions with CYP3A inhibitors have been reported to be weaker. The concentrations of non-CYP3A-dependent statins can also be affected, albeit to a mild degree, especially when used concomitantly with HIV or HCV protease inhibitors, primarily through interaction with OATP1B1; treatment should begin with the lowest effective dose. Efficacy and adverse events should be monitored regularly. Concomitant use of pravastatin with niacin may increase the risk of skeletal muscle adverse reactions; in such cases, dose reduction of pravastatin should be considered.
Because the concurrent use of other fibrates during treatment with HMG-CoA reductase inhibitors is known to increase the risk of myopathy, caution should be exercised when using pravastatin in combination with other fibrates.
Because the concomitant use of HMG-CoA reductase inhibitors with gemfibrozil increases the risk of myopathy/rhabdomyolysis, concomitant use of pravastatin with gemfibrozil should be avoided.
For more complete data on interactions of pravastatin (16 in total), please visit the HSDB record page.

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Non-human toxicity values
Dog (male) oral LD50 >800 mg/kg
Rat (female) subcutaneous LD50 4455 mg/kg
Rat (male) subcutaneous LD50 3172 mg/kg
Rat (female) intravenous LD50 440 mg/kg
For more complete data on non-human toxicity values for pravastatin (out of 12), please visit the HSDB records page.

[1]. Pravastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs. 1991 Jul;42(1):65-89.

[2]. Pravastatin Prevents Increases in Activity of Metalloproteinase-2 and Oxidative Stress, and Enhances Endothelium-Derived Nitric Oxide-Dependent Vasodilation in Gestational Hypertension. Antioxidants (Basel) . 2023 Apr 16;12(4):939.

Therapeutic Uses

Cholesterol-lowering drug; hydroxymethylglutaryl-CoA reductase inhibitor
For patients with hypercholesterolemia and asymptomatic coronary heart disease (CHD), pravastatin (Pravachol) is indicated for: reducing the risk of myocardial infarction, reducing the risk of undergoing myocardial revascularization surgery, and reducing the risk of cardiovascular death without increasing the risk of death from non-cardiovascular causes. /US Product Label Content/
For patients with clinically manifested coronary heart disease (CHD), pravastatin (Pravachol) is indicated for: reducing the risk of all-cause death by reducing coronary heart disease mortality, reducing the risk of myocardial infarction (MI), reducing the risk of undergoing myocardial revascularization surgery, reducing the risk of stroke and stroke/transient ischemic attack (TIA), and slowing the progression of coronary atherosclerosis. /US product label includes/
Pavastatin's indications: As adjunctive therapy to lower total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and triglyceride (TG) levels, and to increase high-density lipoprotein cholesterol (HDL-C) levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson type IIa and IIb). As adjunctive therapy to treat patients with elevated serum triglyceride levels (Fredrickson type IV). For the treatment of patients with primary beta-lipoproteinemia (Fredrickson type III) who have not responded well to dietary therapy. As adjunctive therapy to dietary and lifestyle interventions, pravastatin is indicated for the treatment of children and adolescents aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH) who, after adequate dietary intervention, have: a. maintained LDL-C ≥190 mg/dL, or b. maintained LDL-C ≥160 mg/dL, and have a family history of early-onset cardiovascular disease (CVD), or have two or more other CVD risk factors. /US product label contains/
For more complete data on the therapeutic uses of pravastatin (of 9), please visit the HSDB record page.

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Drug Warning
Rare cases of rhabdomyolysis, followed by myoglobinuria leading to acute renal failure, have been reported with pravastatin and other similar medications. A history of renal impairment may be a risk factor for rhabdomyolysis. Patients with these conditions should be closely monitored for changes in skeletal muscle.
The risk of myopathy increases when statin therapy is taken concurrently with erythromycin, cyclosporine, niacin, or fibrates. However, in three studies involving a total of 100 post-transplant patients (24 kidney transplant recipients and 76 heart transplant recipients), no myopathy or significant elevations in creatine phosphokinase (CPK) levels were observed. These patients received pravastatin 10 to 40 mg in combination with cyclosporine for up to two years. Some patients also received other immunosuppressive therapies. Furthermore, no myopathy was reported in a small-sample clinical trial of pravastatin in combination with niacin. In a trial of pravastatin (40 mg/day) in combination with gemfibrozil (1200 mg/day), although significant CPK elevations occurred in 4 of the 75 patients receiving the combination therapy, and only 1 of the 73 patients in the placebo group developed myopathy, this trial also did not report myopathy. Compared with the placebo group, gemfibrozil monotherapy group, or pravastatin monotherapy group, the combination therapy group showed an increasing trend in the proportion of patients experiencing elevated CPK levels and withdrawing from the trial due to musculoskeletal symptoms. Monotherapy with fibrates may sometimes be associated with myopathy. Combination therapy of pravastatin with fibrates can further alter lipid levels; its benefits should be carefully weighed against the potential risks of this combination therapy. Rare cases of immune-mediated necrotizing myopathy (IMNM) have been reported, an autoimmune myopathy associated with statin use. IMNM is characterized by proximal muscle weakness and elevated serum creatine phosphokinase (CPK) levels that persist even after statin discontinuation; muscle biopsy showing necrotizing myopathy without significant inflammation, and symptom improvement with immunosuppressant use. Simple myalgia has been reported in patients treated with pravastatin. Myopathy is defined as muscle pain or weakness accompanied by creatine phosphokinase (CPK) levels greater than 10 times the upper limit of normal (ULN). The incidence of myopathy is very low (<0.1%) in pravastatin clinical trials. The possibility of myopathy should be considered in any patient presenting with diffuse myalgia, muscle tenderness or weakness, and/or significantly elevated creatine phosphokinase (CPK). Predisposing factors include advanced age (≥65 years), uncontrolled hypothyroidism, and renal impairment. For more complete data on pravastatin (27 total), please visit the HSDB record page. Pharmacodynamics: Pravastatin acts on 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, leading to increased expression of hepatic low-density lipoprotein (LDL) receptors, thereby reducing plasma LDL cholesterol levels. Pravastatin has been shown to significantly reduce circulating total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B levels. In addition, it moderately reduces very low-density lipoprotein cholesterol (VLDL-C) and triglyceride levels, while increasing high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A levels. In clinical trials in patients with a history of myocardial infarction or angina and high total cholesterol levels, pravastatin reduced total cholesterol by 18%, LDL-C by 27%, triglycerides by 6%, and increased HDL-C by 4%. Furthermore, it has been reported to reduce the risk of death from coronary heart disease by 24%. When used in combination with cholestyramine, pravastatin can reduce LDL-C levels by 50%, slow the progression of atherosclerosis, and reduce the risk of myocardial infarction and death.

C₂₃H₃₆O₇

424.53

424.246

81093-37-0

Pravastatin sodium;81131-70-6

54687

Typically exists as solid at room temperature

1.2±0.1 g/cm3

634.5±55.0 °C at 760 mmHg

171.2-173ºC

213.2±25.0 °C

0.0±4.2 mmHg at 25°C

1.555

1.35

4

7

11

30

656

8

C([C@H]1[C@@H](C)C=CC2[C@@H]1[C@H](C[C@@H](C=2)O)OC(=O)[C@@H](C)CC)C[C@@H](O)C[C@@H](O)CC(=O)O

TUZYXOIXSAXUGO-PZAWKZKUSA-N

InChI=1S/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1

(3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid

pravastatin; 81093-37-0; Pravastatinum; Pravastatina; Pravastatine; Eptastatin; Pravachol; Pravator;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)