HMG-CoA reductase [IC50 = 5.6 μM.]

普伐他汀 (CS-514) 是一种他汀类药物，与饮食、运动和减肥相结合，可降低胆固醇并预防心血管疾病[1]。

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普伐他汀钠是普伐他汀的钠盐，具有降低胆固醇和潜在的抗肿瘤活性。普伐他汀竞争性抑制肝羟甲基戊二酰辅酶A （HMG-CoA）还原酶，该酶催化HMG-CoA转化为甲羟戊二酸，这是胆固醇合成的关键步骤。该药物降低血浆胆固醇和脂蛋白水平，并通过抑制干扰素γ刺激的抗原呈递细胞（如人血管内皮细胞）上的MHC II（主要组织相容性复合体II）来调节免疫反应。此外，普伐他汀和其他他汀类药物一样，在多种肿瘤细胞中表现出促凋亡、生长抑制和促分化活性；这些抗肿瘤活性可能部分是由于抑制Ras和Rho gtpase的异戊二烯化以及相关的信号级联反应。

普伐他汀（40 毫克，单剂量）可使健康受试者中人单核细胞来源的巨噬细胞的胆固醇合成减少 62%，使高胆固醇血症患者减少 47%。普伐他汀（40 毫克/天，8 周）可抑制高胆固醇血症患者的胆固醇合成 55%，并使 LDL 降解增加 57%。普伐他汀 (30 mg/kg/d) 可使接受照射的雄性 Wistar 大鼠营养不良病变长度缩短 34%，肌肉结构恢复，与 CCN2 水平降低相关。

血浆脂质过氧化水平的测定[2] 脂质过氧化产物采用硫代巴比妥酸（TBA）反应物质（TBARS）法，检测脂质过氧化的主要产物丙二醛（MDA）水平。简单地说，将100µL血浆加入试管中，与100µL蒸馏水、50µL 8.1%十二烷基硫酸钠（SDS）、375µL 20%乙酸和375µL 0.8% TBA在95°C水浴中孵育1小时。然后，将样品以4000 rpm离心10 min。将TBA加入样品中，立即得到比色反应，如前所述，通过532 nm波长测量。血浆MDA水平以nmol/mL表示。

血管反应性[2] 解剖腹主动脉段，切成4个环（3mm），其中2个环机械去除内皮，2个环保留内皮。每个主动脉环挂在两个钢丝钩之间，放入含有Krebs-Henseleit溶液(NaCl 130；氯化钾4.7;氯化钙1.6;KH2PO4 1.2;MgSO4 1.2;NaHCO3 15;葡萄糖11.1;（mmol/L）在pH 7.4和37℃条件下，用95% O2和5% CO2起泡，然后在1.5 g的基张力下稳定。[2] 在主动脉环平衡后，通过给药KCl （96 mM）获得KCl最大收缩量，以检测主动脉活力。为了检测内皮功能，用10−6 M的苯肾上腺素（Phe）预收缩主动脉环，并增加浓度（10−9至10−4 M）的乙酰胆碱（ACh）。为了证实内皮源性no依赖性血管舒张的参与，在与Phe预收缩的主动脉环中，在n ω-硝基- l -精氨酸甲酯（L-NAME, 3 × 10−4 M）存在的情况下，获得了对ACh的浓度响应曲线。对得到的浓度-效应曲线进行非线性回归（变斜率），得到了Rmax（最大反应）和pEC50（引起最大反应50%的浓度的负对数）。松弛曲线用松弛对ph诱导收缩的百分比表示，如前所述。[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 60-90 min after oral administration and it presents a low bioavailability of 17%. This low bioavailability can be presented due to the polar nature of pravastatin which produces a high range of first-pass metabolism and incomplete absorption. Pravastatin is rapidly absorbed from the upper part of the small intestine via proton-coupled carrier-mediated transport to be later taken up in the livery by the sodium-independent bile acid transporter. The reported time to reach the peak serum concentration in the range of 30-55 mcg/L is of 1-1.5 hours with an AUC ranging from 60-90 mcg.h/L.
From the administered dose of pravastatin, about 70% is eliminated in the feces while about 20% is obtained in the urine. When pravastatin is administered intravenously, approximately 47% of the administered dose is eliminated via the urine with 53% of the dose eliminated either via biotransformation of biliary.
The reported steady-state volume of distribution of pravastatin is reported to be of 0.5 L/kg. This pharmacokinetic parameter in children was found to range from 31-37 ml/kg.
The reported clearance rate of pravastatin ranges from 6.3-13.5 ml.min/kg in adults while in children it has been reported to be of 4-11 L/min.
/MILK/ In lactating rats, up to 7 times higher levels of pravastatin are present in the breast milk than in the maternal plasma, which corresponds to exposure 2 times the MRHD of 80 mg/day based on body surface area (mg/sq m).
In pregnant rats, pravastatin crosses the placenta and is found in fetal tissue at 30% of the maternal plasma levels following administration of a single dose of 20 mg/day orally on gestation day 18, which corresponds to exposure 2 times the MRHD of 80 mg daily based on body surface area (mg/ssq m).
Low levels of radioactivity were found in the fetuses of rats dosed orally with radiolabeled pravastatin sodium.
Dogs are unique as compared to all other species tested, including man, in that they have a much greater systemic exposure to pravastatin. Pharmacokinetic data from a study in dogs at a dose of 1.1 mg/kg (comparable to a 40 mg dose in humans) showed that the elimination of pravastatin is slower in dogs than in humans. Absolute bioavailability is two times greater in dogs compared to humans and estimated renal and hepatic extraction of pravastatin are about one-tenth and onehalf, respectively, than those in humans. When concentrations of pravastatin in plasma or serum of rats, dogs, rabbits, monkeys and humans were compared, the exposure in dogs was dramatically higher, based on both CMAX and AUC. The mean AUC value in man at a therapeutic dose of 40 mg is approximately 100 times less than that in the dog at the no-effect dose of 12.5 mg/kg, and approximately 180 times lower than that in dogs at the threshold dose of 25 mg/kg for cerebral hemorrhage.
For more Absorption, Distribution and Excretion (Complete) data for Pravastatin (23 total), please visit the HSDB record page.

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Metabolism / Metabolites
After initial administration, pravastatin undergoes extensive first-pass extraction in the liver. However, pravastatin's metabolism is not related to the activity of the cytochrome P-450 isoenzymes and its processing is performed in a minor extent in the liver. Therefore, this drug is highly exposed to peripheral tissues. The metabolism of pravastatin is ruled mainly by the presence of glucuronidation reactions with very minimal intervention of CYP3A enzymes. After metabolism, pravastatin does not produce active metabolites. This metabolism is mainly done in the stomach followed by a minor portion of renal and hepatic processing. The major metabolite formed as part of pravastatin metabolism is the 3-alpha-hydroxy isomer. The activity of this metabolite is very clinically negligible.
The major biotransformation pathways for pravastatin are: (a) isomerization to 6-epi pravastatin and the 3a-hydroxyisomer of pravastatin (SQ 31,906) and (b) enzymatic ring hydroxylation to SQ 31,945. The 3a-hydroxyisomeric metabolite (SQ 31,906) has 1/10 to 1/40 the HMG-CoA reductase inhibitory activity of the parent compound. Pravastatin undergoes extensive first-pass extraction in the liver (extraction ratio 0.66).

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

Toxicity Summary
IDENTIFICATION AND USE: Pravastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin), is an antilipemic agent. Pravastatin occurs as an odorless, white to off-white, fine or crystalline powder formulated into a tablet. It is used as an adjunct to lifexstyle modifications for prevention of cardiovascular events and for the management of dyslipidemias. HUMAN EXPOSURE AND TOXICITY: Pravastatin is contraindicated for use in pregnant woman because of the potential for fetal harm. There have also been rare reports of fatal and non-fatal hepatic failure in patients taking statins, including pravastatin. Also, rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with pravastatin and other drugs in this class. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. ANIMAL STUDIES: Acute studies were performed in both mice and rats. Signs of toxicity in mice were decreased activity, irregular respiration, ptosis, lacrimation, soft stool, diarrhea, urine-stained abdomen, ataxia, creeping behavior, loss of righting reflex, hypothermia, urinary incontinence, pilo-erection convulsion and/or prostration. Signs of toxicity in rats were soft stool, diarrhea, decreased activity, irregular respiration, waddling gait, and ataxia, loss of righting reflex and/or weight loss. In a 2-year study in rats fed pravastatin at doses of 10, 30, or 100 mg/kg bw, there was an increased incidence of hepatocellular carcinomas in males at the highest dose. Likewise, in a 2-year study in mice fed pravastatin at doses of 250 and 500 mg/kg/day, there was an increased incidence of hepatocellular carcinomas in males and females; lung adenomas in females were increased. In dogs, pravastatin sodium was toxic at high doses and caused cerebral hemorrhage with clinical evidence of acute CNS toxicity such as ataxia, convulsions. The threshold dose for CNS toxicity is 25 mg/kg. Cerebral hemorrhages have not been observed in any other laboratory species and the CNS toxicity in dogs may represent a species-specific effect. In pregnant rats given oral gavage doses of 4, 20, 100, 500, and 1000 mg/kg/day from gestation days 7 through 17 (organogenesis) increased mortality of offspring and increased cervical rib skeletal anomalies were observed at >/= 100 mg/kg/day. In pregnant rats given oral gavage doses of 10, 100, and 1000 mg/kg/day from gestation day 17 through lactation day 21 (weaning), increased mortality of offspring and developmental delays were observed at >/= 100 mg/kg/day. In a fertility study in adult rats with daily doses up to 500 mg/kg, pravastatin did not produce any adverse effects on fertility or general reproductive performance. No evidence of mutagenicity was observed in vitro, with or without metabolic activation, in the following studies: microbial mutagen tests, using mutant strains of Salmonella typhimurium or Escherichia coli; a forward mutation assay in L5178Y TK +/- mouse lymphoma cells; a chromosomal aberration test in hamster cells; and a gene conversion assay using Saccharomyces cerevisiae. In addition, there was no evidence of mutagenicity in either a dominant lethal test in mice or a micronucleus test in mice.

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Hepatotoxicity
Pravastatin therapy is associated with mild, asymptomatic and usually transient serum aminotransferase elevations. In summary analyses of large scale studies with prospective monitoring, ALT elevations above normal occurred in 3% to 7% of patients; but levels above 3 times the upper limit of normal (ULN) occurred in less than 1.2% of both pravastatin- as well as in placebo-treated subjects. Most of these elevations were self-limited and did not require dose modification. Pravastatin has been only rarely associated with clinically apparent hepatic injury with symptoms or jaundice at a rate estimated to be 1 per 100,000 users or less. In the case reports, latency varied from 2 to 9 months and the pattern of serum enzyme elevations from cholestatic to hepatocellular. Recovery was complete within a few months. Rash, fever and eosinophilia were uncommon as were autoantibodies, but few cases have been reported and the full clinical syndrome not well defined. Pravastatin appears to be less likely to cause clinically apparent liver injury than atorvastatin, simvastatin and rosuvastatin.
Likelihood score: B (likely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Levels of pravastatin in milk are low, but no relevant published information exists with its use during breastfeeding. The consensus opinion is that women taking a statin should not breastfeed because of a concern with disruption of infant lipid metabolism. However, others have argued that children homozygous for familial hypercholesterolemia are treated with statins beginning at 1 year of age, that statins have low oral bioavailability, and risks to the breastfed infant are low, especially with pravastatin and rosuvastatin. Until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Due its polarity, pravastatin binding to plasma proteins is very limited and the bound form represents only about 43-48% of the administered dose. However, the activity of p-glycoprotein in luminal apical cells and OATP1B1 produce significant changes to pravastatin distribution and elimination.

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Interactions
The HMG-CoA reductase inhibitors are a class of drugs also known as statins. These drugs are effective and widely prescribed for the treatment of hypercholesterolemia and prevention of cardiovascular morbidity and mortality. Seven statins are currently available: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Although these drugs are generally well tolerated, skeletal muscle abnormalities from myalgia to severe lethal rhabdomyolysis can occur. Factors that increase statin concentrations such as drug-drug interactions can increase the risk of these adverse events. Drug-drug interactions are dependent on statins' pharmacokinetic profile: simvastatin, lovastatin and atorvastatin are metabolized through cytochrome P450 (CYP) 3A, while the metabolism of the other statins is independent of this CYP. All statins are substrate of organic anion transporter polypeptide 1B1, an uptake transporter expressed in hepatocyte membrane that may also explain some drug-drug interactions. Many HIV-infected patients have dyslipidemia and comorbidities that may require statin treatment. HIV-protease inhibitors (HIV PIs) are part of recommended antiretroviral treatment in combination with two reverse transcriptase inhibitors. All HIV PIs except nelfinavir are coadministered with a low dose of ritonavir, a potent CYP3A inhibitor to improve their pharmacokinetic properties. Cobicistat is a new potent CYP3A inhibitor that is combined with elvitegravir and will be combined with HIV-PIs in the future. The HCV-PIs boceprevir and telaprevir are both, to different extents, inhibitors of CYP3A. This review summarizes the pharmacokinetic properties of statins and PIs with emphasis on their metabolic pathways explaining clinically important drug-drug interactions. Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated. Atorvastatin is also a CYP3A substrate, but less potent drug-drug interactions have been reported with CYP3A inhibitors. Non-CYP3A-dependent statin concentrations are also affected although to a lesser extent when coadministered with HIV or HCV PIs, mainly through interaction with OATP1B1, and treatment should start with the lowest available statin dose. Effectiveness and occurrence of adverse effects should be monitored at regular time intervals.
The risk of skeletal muscle effects may be enhanced when pravastatin is used in combination with niacin; a reduction in Pravachol dosage should be considered in this setting.
Because it is known that the risk of myopathy during treatment with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is increased with concurrent administration of other fibrates, Pravachol should be administered with caution when used concomitantly with other fibrates
Due to an increased risk of myopathy/rhabdomyolysis when hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are coadministered with gemfibrozil, concomitant administration of Pravachol with gemfibrozil should be avoided
For more Interactions (Complete) data for Pravastatin (16 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Dog (male) oral >800 mg/kg
LD50 Rat (female) sc 4455 mg/kg
LD50 Rat (male) sc 3172 mg/kg
LD50 Rat (female) iv 440 mg/kg
For more Non-Human Toxicity Values (Complete) data for Pravastatin (12 total), please visit the HSDB record 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
Anticholesteremic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors
In hypercholesterolemic patients without clinically evident coronary heart disease (CHD), Pravachol (pravastatin sodium) is indicated to: reduce the risk of myocardial infarction, reduce the risk of undergoing myocardial revascularization procedures and reduce the risk of cardiovascular mortality with no increase in death from non-cardiovascular causes. /Included in US product label/
In patients with clinically evident coronary heart disease (CHD), Pravachol is indicated to: reduce the risk of total mortality by reducing coronary death, reduce the risk of myocardial infarction (MI), reduce the risk of undergoing myocardial revascularization procedures, reduce the risk of stroke and stroke/transient ischemic attack (TIA) and slow the progression of coronary atherosclerosis. /Included in US product label/
Pravachol is indicated: As an adjunct to diet to reduce elevated 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) in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb). As an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson Type IV). For the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who do not respond adequately to diet. As an adjunct to diet and lifestyle modification for treatment of heterozygous familial hypercholesterolemia (HeFH) in children and adolescent patients ages 8 years and older if after an adequate trial of diet the following findings are present: a. LDL-C remains >/=190 mg/dL or b. LDL-C remains >/=160 mg/dL and there is a positive family history of premature cardiovascular disease (CVD) or two or more other CVD risk factors are present in the patient. /Included in US product label/
For more Therapeutic Uses (Complete) data for Pravastatin (9 total), please visit the HSDB record page.

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Drug Warnings
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with pravastatin and other drugs in this class. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects.
The risk of myopathy during treatment with statins is increased with concurrent therapy with either erythromycin, cyclosporine, niacin, or fibrates. However, neither myopathy nor significant increases in CPK levels have been observed in 3 reports involving a total of 100 post-transplant patients (24 renal and 76 cardiac) treated for up to 2 years concurrently with pravastatin 10 to 40 mg and cyclosporine. Some of these patients also received other concomitant immunosuppressive therapies. Further, in clinical trials involving small numbers of patients who were treated concurrently with pravastatin and niacin, there were no reports of myopathy. Also, myopathy was not reported in a trial of combination pravastatin (40 mg/day) and gemfibrozil (1200 mg/day), although 4 of 75 patients on the combination showed marked CPK elevations versus 1 of 73 patients receiving placebo. There was a trend toward more frequent CPK elevations and patient withdrawals due to musculoskeletal symptoms in the group receiving combined treatment as compared with the groups receiving placebo, gemfibrozil, or pravastatin monotherapy. The use of fibrates alone may occasionally be associated with myopathy. The benefit of further alterations in lipid levels by the combined use of Pravachol with fibrates should be carefully weighed against the potential risks of this combination.
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum CPK, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation and improvement with immunosuppressive agents.
Uncomplicated myalgia has ... been reported in pravastatin-treated patients. Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the ULN, was rare (<0.1%) in pravastatin clinical trials. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Predisposing factors include advanced age (>/= 65), uncontrolled hypothyroidism, and renal impairment.
For more Drug Warnings (Complete) data for Pravastatin (27 total), please visit the HSDB record page.

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Pharmacodynamics
The action of pravastatin on the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase produces an increase in the expression of hepatic LDL receptors which in order decreases the plasma levels of LDL cholesterol. The effect of pravastatin has been shown to significantly reduce the circulating total cholesterol, LDL cholesterol, and apolipoprotein B. As well, it modestly reduces very low-density-lipoproteins (VLDL) cholesterol and triglycerides while increasing the level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A. In clinical trials with patients with a history of myocardial infarction or angina with high total cholesterol, pravastatin decreased the level of total cholesterol by 18%, decreased of LDL by 27%, decreased of triglycerides by 6% and increased of high-density lipoprotein (HDL) by 4%. As well, there was reported a decrease in risk of death due to coronary disease of 24%. When coadministered with [cholestyramine], pravastatin can reduce by 50% the levels of LDL and slow the progression of atherosclerosis and 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

127.12

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。