Pitavastatin suppresses the development of a panel of ovarian cancer cells cultured as spheroids (IC50 = 0.6-4 μM) or as monolayers (IC50 = 0.4-5 μM), including those thought to most likely represent HGSOC[4]. The increased activity of executioner caspases-3,7, as well as caspase-8 and caspase-9 in Ovcar-8 cells and Ovcar-3 cells, indicates that pitavastatin (one microgram; 48 hours) triggers apoptosis[4]. Ovcar-8 cells cleave PARP when exposed to 1 μM pitavastatin for 48 hours[4]. In TNF-stimulated human saphenous vein endothelial cells, pitavastatin (0.1 and 1 μM; 1 h, followed by 6 h of TNF-α incubation) enhances the production of ICAM-1 mRNA by inhibiting the NF-κB pathway[6].

Depressant pitavastatin (59 mg/kg; po; twice daily for 28 days) significantly reduces tumor growth[4]. In a rabbit model of diet-induced severe hyperlipidemia, pitavastatin (0.1 mg/kg; po; daily for 12 weeks) slows the development of atherosclerosis and increases NO bioavailability through eNOS up-regulation and O2-depletion[7].

Western Blot Analysis[4]
Cell Types: Ovcar-8 cells
Tested Concentrations: 1 μM
Incubation Duration: 48 hrs (hours)
Experimental Results: Induced PARP cleavage.

Animal/Disease Models: 4 week old female NCR Nu/Nu female mice (bearing Ovcar-4 tumours)[4]
Doses: 59 mg/kg
Route of Administration: po ; twice (two times) daily for 28 days
Experimental Results: Caused significant tumor regression.

---

Animal/Disease Models: Female New Zealand white rabbits (diet induced severe hyperlipidemia)[7]
Doses: 0.1 mg/kg
Route of Administration: po; daily for 12 weeks
Experimental Results: Retarded the progression of atherosclerosis formation and improved NO bioavailability by eNOS up-regulation and decrease of O2-.

Absorption, Distribution and Excretion
Peak plasma concentrations of pitavastatin are reached approximately 1 hour after oral administration. With a single dose of 1 mg to 24 mg pitavastatin once daily, both Cmax and AUC0-inf show approximately dose-proportional increases. The absolute bioavailability of pitavastatin oral solution is 51%. There is no significant difference in Cmax and AUC between morning and evening administration. In healthy volunteers, the percentage change in LDL-C from baseline after an evening dose of 4 mg pitavastatin was slightly higher than that after a morning dose. Pitavastatin is primarily absorbed in the small intestine, with minimal absorption in the colon. Co-administration of pitavastatin with a high-fat meal (50% fat content) reduces Cmax by 43% but does not significantly reduce AUC. Compared to other statins, pitavastatin has relatively high bioavailability, which is attributed to enterohepatic reabsorption after intestinal absorption. Genetic variations in the liver transport protein OATP1B1 (organic anion transport polypeptide 1B1), encoded by the SCLCO1B1 gene (a member of the solute carrier organic anion transporter family 1B1), have been shown to affect the pharmacokinetics of pitavastatin. Pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) in the OATP1B1 (SLCO1B1) gene showed that the pitavastatin AUC was 3.08-fold higher in homozygous individuals of the 521CC genotype compared to those of homozygous individuals of the 521TT genotype. Other statins affected by this polymorphism include simvastatin, pitavastatin, atorvastatin, and rosuvastatin. Individuals carrying the 521CC genotype may face a higher risk of dose-related adverse events, including myopathy and rhabdomyolysis, due to increased drug exposure. Following a single oral dose of 32 mg of 14C-labeled pitavastatin, an average of 15% of the radioactivity is excreted in the urine, while an average of 79% of the dose is excreted in the feces over 7 days. [L48616]
The mean volume of distribution is approximately 148 L.
The apparent mean oral clearance of pitavastatin after a single dose is 43.4 L/h.
/Breast Milk/ It is unclear whether pitavastatin is secreted into human breast milk, but studies have shown that small amounts of similar drugs do enter breast milk. Rat studies have shown that pitavastatin is secreted into breast milk.
This study aimed to understand the mechanism by which variations in the SLCO1B1 gene, encoding the OATP1B1 (organic anion transporter polypeptide) transporter, affect the transport activity of two OATP1B1 substrates—pravastatin and pitavastatin—and their impact on substrate distribution. This study measured the uptake of pravastatin, pitavastatin, and fluvastatin in oocytes overexpressing SLCO1B11a and SLCO1B115 to compare changes in in vitro transport activity. After administering 40 mg of pravastatin or 4 mg of pitavastatin to 11 healthy volunteers with homozygous SLCO1B11a/1a and SLCO1B115/15 genotypes, the pharmacokinetic parameters of pravastatin and pitavastatin were compared between the two genotypes. Compared to the homozygous SLCO1B115 genotype, SLCO1B115-overexpressing oocytes showed decreased uptake of pravastatin and pitavastatin, while fluvastatin uptake remained unchanged. Compared to the homozygous SLCO1B11a genotype, the fold change in the intrinsic clearance (Clint) of pitavastatin in the SLCO1B115 homozygous genotype was greater than that of pravastatin (P<0.0001). Compared to pravastatin, the clearance (Cl/F) of pitavastatin in vivo was significantly lower in subjects carrying the SLCO1B115/15 genotype (P<0.01), consistent with in vitro findings. Therefore, the SLCO1B115 variant leads to an increase in the area under the plasma concentration-time curve (AUC) of these non-metabolizable substrates. However, compared to SLCO1B11a, the reduction in pitavastatin transport activity was greater in the SLCO1B115 variant, which is related to the fact that the SLCO1B1 gene polymorphism has a greater effect on the pharmacokinetics of pitavastatin than on pravastatin. This study suggests that the substrate dependence of the SLCO1B115 variant may regulate the effect of SLCO1B1 polymorphisms on the metabolism of pitavastatin and pravastatin in vivo. This study employed an open-label, randomized, three-period crossover design to conduct pharmacokinetic studies in 12 Chinese volunteers after single administrations of 1 mg, 2 mg, and 4 mg of pitavastatin calcium. Plasma concentrations of pitavastatin acid and pitavastatin lactone were determined using high-performance liquid chromatography (HPLC). Single nucleotide polymorphisms (SNPs) of ABCB1, ABCG2, SLCO1B1, CYP2C9, and CYP3A5 were detected using TaqMan (MGB) genotyping. The relationships between these SNPs and dose-normalized (based on a 1 mg dose) area under the plasma concentration-time curve (AUC_0-∞) and peak plasma concentrations (C_max) of pitavastatin acid and lactone forms were analyzed. Pitavastatin exhibited linear pharmacokinetic characteristics with significant inter-individual variability. Compared to CYP2C91/1 genotype carriers, CYP2C91/3 genotype carriers had higher AUC_0-∞ and C_max values for pitavastatin acid and pitavastatin lactone (P<0.05). For the ABCB1 G2677T/A mutation, non-G genotype carriers had higher C_max and AUC_0-∞ values for pitavastatin acid and pitavastatin lactone than GT, GA, or GG genotype carriers (P<0.05). The dose-effects of the SLCO1B1 c.521T>C and g.11187G>A genes were observed to influence the pharmacokinetics of both the acid and lactone forms. Compared with non-SLCO1B117 carriers, SLCO1B117 carriers had higher Cmax and AUC(0-∞) values for both the acid and lactone forms of the drug (P<0.05). Significant sex differences were observed in the pharmacokinetics of the lactone form. Female SLCO1B1 521TT subjects had higher pitavastatin Cmax and AUC(0-∞) values than male 521TT subjects, but this sex difference disappeared in 521TC and 521CC subjects. The pharmacokinetics of pitavastatin were not significantly affected by ABCB1 C1236T, ABCB1C3435T, CYP3A53, ABCG2 c.34G > A, c.421C > A, SLCO1B1 c.388A>G, c.571T>C, and c.597C>T. We conclude that CYP2C93, ABCB1 G2677T/A, SLCO1B1 c.521T>C, SLCO1B1 g.11187G > A, SLCO1B117, and sex are factors contributing to inter-individual variability in pitavastatin pharmacokinetics. Individualized treatment is necessary for patients with hypercholesterolemia taking pitavastatin. Pitavastatin is over 99% protein-bound in human plasma, primarily binding to albumin and α1-acid glycoprotein, with a mean volume of distribution of approximately 148 liters. Pitavastatin and/or its metabolites bind minimally to blood cells. For more complete data on the absorption, distribution, and excretion of pitavastatin (12 items in total), please visit the HSDB records page. Metabolism/Metabolites The primary metabolic pathway of pitavastatin involves glucuronidation via hepatic uridine 5'-bisphosphoglucuronyltransferase (UGT), subsequently producing pitavastatin lactone. The cytochrome P450 system plays a minimal role in the metabolism of pitavastatin. Pitavastatin is primarily metabolized via CYP2C9, with a small amount metabolized via CYP2C8. Its main metabolite in human plasma is a lactone, which is formed by the catalytic binding of pitavastatin to glucuronide esters by UGT (UGT1A3 and UGT2B7). Researchers have investigated the effects of pitavastatin on hepatic microsomal drug metabolism in rats and measured the activities of various drug-metabolizing enzymes. After repeated administration of pitavastatin at doses of 1–10 mg/kg/day for 7 consecutive days, no induction of drug-metabolizing enzymes (aniline hydroxylase, aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase, and UDP-glucuronyltransferase) was observed in the pitavastatin group compared to the control group. Based on various in vitro experimental methods, it was concluded that CYP2C9 is the enzyme responsible for pitavastatin metabolism, and its metabolites were not detected in renal and intestinal microsomes. CYP2C9 polymorphism is not related to pitavastatin metabolism. No inhibition of 4-hydroxylation of tolbutamide (CYP2C9) and 6β-hydroxylation of testosterone (CYP3A4) was detected in the presence of pitavastatin. The results indicate that pitavastatin does not affect the drug metabolism system. Pitavastatin is primarily metabolized via CYP2C9, and secondarily via CYP2C8. In human plasma, the major metabolite of pitavastatin is lactone, which is formed from ester-type pitavastatin glucuronide conjugates catalyzed by uridine diphosphate (UDP) glucuronyl transferases (UGT1A3 and UGT2B7). To elucidate potential species differences, we investigated the in vitro metabolism of pitavastatin and its lactones using liver and kidney microsomes from rats, dogs, rabbits, monkeys, and humans. Upon addition of UDP-glucuronic acid to liver microsomes, pitavastatin lactone was identified as the major metabolite in a variety of animals, including humans. The metabolic clearance of pitavastatin and its lactones in monkey liver microsomes was significantly higher than in humans. M4 is a 3-dehydroxyl metabolite of pitavastatin that is converted to its lactone form and pitavastatin in monkey liver microsomes in the presence of UDP-glucuronic acid. These results indicate that lactation is a common metabolic pathway for drugs such as 5-hydroxyvalerate derivatives. Due to its structural characteristics, the acid form of the drug is metabolized to the lactone form. UDP-glucuronyltransferase is the key enzyme in the lactation of pitavastatin, and its overall metabolism differs from that in humans due to the extensive oxidative metabolism of pitavastatin and its lactone in monkeys.

---

Biological half-life
The mean plasma elimination half-life is approximately 12 hours. [L48616]
After a single oral dose of 32 mg (14)C-labeled pitavastatin, an average of 15% of the radioactive material is excreted in the urine, while an average of 79% of the dose is excreted in the feces within 7 days. The mean plasma elimination half-life is approximately 12 hours.

Toxicity Summary
Identification and Use: Pitavastatin is a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., a statin) and belongs to the lipid-lowering drug class. It is used in combination with lifestyle interventions to treat dyslipidemia. Human Exposure and Toxicity: Pitavastatin is contraindicated in pregnant women or patients with active liver disease, including unexplained persistent elevations in serum transaminases. HMG-CoA reductase inhibitors, including pitavastatin, have been reported to cause myopathy and rhabdomyolysis, leading to acute renal failure secondary to myoglobinuria. These risks can occur at any dose level but increase with increasing dose. Rare cases of fatal and non-fatal hepatic failure have also been reported in patients treated with pitavastatin. Animal Studies: In a 92-week mouse carcinogenicity study, no drug-related tumors were observed in mice administered pitavastatin at the maximum tolerated dose of 75 mg/kg/day. However, in a 92-week rat carcinogenicity study, rats were administered pitavastatin by gavage at doses of 1, 5, and 25 mg/kg/day. The results showed a significantly increased incidence of thyroid follicular cell tumors in the 25 mg/kg/day dose group. During organogenesis in pregnant rats, embryo-fetal development studies were conducted by gavage administration of pitavastatin at doses of 3, 10, and 30 mg/kg/day. No adverse reactions were observed in the 3 mg/kg/day dose group. During organogenesis in pregnant rabbit fetuses, embryo-fetal development studies were conducted by gavage administration of pitavastatin at doses of 0.1, 0.3, and 1 mg/kg/day. Maternal toxicity, manifested as weight loss and abortion, was observed at all tested doses. In perinatal/postpartum studies, pregnant rats were administered pitavastatin by gavage at doses of 0.1, 0.3, 1, 3, 10, and 30 mg/kg/day from organogenesis to weaning. Results showed maternal death in the 0.3 mg/kg/day dose group, lactation disorders in all dose groups, and reduced neonatal pup survival rates in all dose groups. Oral doses of 10 and 30 mg/kg/day had no adverse effects on fertility in male and female rats. Pitavastatin did not show mutagenicity in the Ames test with or without metabolically activated Salmonella typhimurium and Escherichia coli, the micronucleus test after a single dose in mice and multiple doses in rats, the unplanned DNA synthesis test in rats, and the comet test in mice. Chromosomal breakage was observed at the highest tested dose in the chromosome aberration test, along with high levels of cytotoxicity.
Hepatotoxicity
Compared to other more widely used statins, information regarding the potential hepatotoxicity of pitavastatin is limited. In large clinical trials, pitavastatin treatment was associated with mild, asymptomatic, and usually transient elevations in serum transaminases in approximately 1% of patients, but elevations exceeding the upper limit of normal (ULN) by more than 3 times were uncommon, and no clinically significant cases of hepatitis were reported in pre-registration clinical trials. However, since pitavastatin's market launch, the sponsor has received reports of jaundice, hepatitis, and liver failure (including deaths). However, the published literature has not clearly defined the clinical features and typical course of pitavastatin-related liver injury. On the other hand, other statins have been associated with clinically significant acute liver injury, typically occurring 1 to 6 months after treatment, with serum enzyme elevations presenting as cholestatic or hepatocellular. Rash, fever, and eosinophilia are uncommon, but some cases have autoimmune features, including autoantibodies, liver biopsy showing chronic hepatitis, and clinical response to corticosteroid therapy. This pattern has not yet been confirmed with pitavastatin.
Probability Score: D (Possibly a rare, clinically significant cause of liver injury).

---

Effects during pregnancy and lactation
◉ Overview of medication use during lactation
There is currently no publicly available information regarding the use of pitavastatin during lactation. Pitavastatin binds to plasma proteins at a rate as high as 99%, therefore its concentration in breast milk is likely to be very low. Due to concerns about disrupting lipid metabolism in infants, it is generally believed that pitavastatin should not be used during lactation. However, some argue that children homozygous for familial hypercholesterolemia who have received statin therapy from age 1, with low oral bioavailability of statins, pose a low risk to breastfed infants, especially rosuvastatin and pravastatin. Until more data are available, especially during the breastfeeding period for newborns or premature 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. Protein Binding Pitavastatin has a protein binding rate of over 99% in human plasma, primarily binding to albumin and α1-acid glycoprotein. Interactions Pitavastatin is a substrate of organic anion transport polypeptide (OATP) 1B1 (OATP2). Drugs that inhibit OATP1B1 (e.g., cyclosporine, erythromycin, rifampin) can improve the bioavailability of pitavastatin. Concomitant use of pitavastatin (2 mg once daily) with ezetimibe (10 mg for 7 days) decreased peak plasma concentration and AUC of pitavastatin by 2% and 0.2%, respectively, while increasing peak plasma concentration and AUC of ezetimibe by 9% and 2%, respectively. Erythromycin can significantly increase pitavastatin exposure. ¹ When pitavastatin (4 mg once daily on day 4) was co-administered with erythromycin (500 mg four times daily for 6 days), the peak plasma concentration and AUC of pitavastatin increased by 3.6-fold and 2.8-fold, respectively; these effects were considered clinically significant. The interaction between pitavastatin and erythromycin may be partly due to the inhibition of pitavastatin hepatic uptake mediated by erythromycin-induced organic anion transporter polypeptide (OATP) 1B1. If co-administered with erythromycin, the dose of pitavastatin should not exceed 1 mg once daily.
When pitavastatin (4 mg once daily on days 1–5 and 11–15) was co-administered with extended-release diltiazem hydrochloride (240 mg once daily on days 6–15), the peak plasma concentration and AUC of pitavastatin increased by 15% and 10%, respectively, while the peak plasma concentration and AUC of diltiazem decreased by 7% and 2%, respectively. For more complete data on interactions with pitavastatin (20 items in total), please visit the HSDB records page.

[1]. Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. J Atheroscler Thromb. 2000;7(3):138-44.

[2]. Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes. Circulation. 2014 Feb 25;129(8):896-906.

[3]. Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice. Cardiovasc Drugs Ther. 2013 Oct;27(5):413-24.

[4]. Pitavastatin decreases tau levels via the inactivation of Rho/ROCK. Neurobiol Aging. 2012 Oct;33(10):2306-20.

[5]. Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer.Sci Rep. 2017 Jul 14;7(1):5410.

[6]. The Effects of Pitavastatin on Nuclear Factor-Kappa B and ICAM-1 in Human Saphenous Vein Graft Endothelial Culture. Cardiovasc Ther. 2019 May 2;2019:2549432.

[7]. A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits. Atherosclerosis. 2004 Oct;176(2):255-63.

[8]. A comprehensive review on the lipid and pleiotropic effects of pitavastatin. Prog Lipid Res. 2021 Nov;84:101127.

Therapeutic Uses
Rivalo (Hydroxymethylglutaryl-CoA reductase inhibitor) is indicated as an adjunct to diet therapy to lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG) in adult patients with primary hyperlipidemia or mixed dyslipidemia, and to increase high-density lipoprotein cholesterol (HDL-C). /Included on US product label/ The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines recommend statins as first-line treatment for the prevention of atherosclerotic cardiovascular disease (ASCVD) in adults. Pitavastatin can be used for primary or secondary prevention in adults when moderate-intensity statin therapy is required. /Not included on US product label/ /Therapeutic Use/ Pitavastatin generally functions as a cholesterol-lowering drug. Previously, pitavastatin was found to have anti-glioma stem cell properties through drug screening. However, its use in the treatment of liver cancer cells has not been reported. This study analyzed the cytotoxicity of pitavastatin on hepatocellular carcinoma cells using cell viability and colony formation assays. Changes in the cell cycle after pitavastatin treatment were examined, along with the expression of apoptosis-related proteins and the effects of caspase inhibitors. The in vivo inhibitory effect of pitavastatin on liver tumor growth was also tested. Results showed that pitavastatin inhibited the growth and colony formation of Huh-7 and SMMC7721 hepatocellular carcinoma cells and induced G1 phase arrest in hepatocellular carcinoma cells. The proportion of cells in the sub-G1 phase increased after pitavastatin treatment. Pitavastatin promoted the lysis of caspase-9 and caspase-3 in hepatocellular carcinoma cells. The caspase inhibitor Z-VAD-FMK reversed the cytotoxic effects of pitavastatin. Furthermore, pitavastatin inhibited tumor growth and improved the survival rate of tumor-bearing mice. This study suggests that the existing drug pitavastatin has anti-hepatocellular carcinoma activity and holds promise for development as a therapeutic agent for liver cancer.
Drug Warning

Elevated serum transaminase (AST [SGOT], ALT [SGPT]) levels have been reported in patients taking statins (including pitavastatin). These elevations are usually transient and resolve or improve with continued treatment or temporary discontinuation of the drug. In a Phase II placebo-controlled study, 0.5% of patients taking 4 mg pitavastatin daily experienced serum ALT levels exceeding three times the upper limit of normal. Post-marketing surveillance has shown rare cases of fatal and non-fatal liver failure in patients taking statins (including pitavastatin).
Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy that is also rare in patients taking statins. IMN is characterized by proximal muscle weakness and elevated creatine kinase (CK, creatine phosphokinase, CPK) levels that persist even after discontinuation of statins; necrotizing myopathy without significant inflammation; and improvement in symptoms with immunosuppressant therapy. Pitavastatin should be used with caution in patients with predisposing factors for myopathy (e.g., advanced age [over 65 years], renal insufficiency, inadequate treatment of hypothyroidism), and in patients receiving certain lipid-lowering medications (e.g., fibrates, lipid-lowering doses of niacin).
HMG-CoA reductase inhibitors (including rivaroxalate) have been reported to cause myopathy and rhabdomyolysis, leading to secondary myoglobinuria and acute renal failure. These risks can occur at any dose level but increase with increasing dose.
Pitavastatin is excreted into rat milk. It is currently unknown whether pitavastatin is excreted into human milk; however, other statins are excreted in small amounts into human milk. Because pitavastatin can cause serious adverse reactions in nursing infants, it is contraindicated in breastfeeding women. Women receiving pitavastatin treatment should be advised not to breastfeed their infants or to discontinue pitavastatin. For more complete data on drug warnings for pitavastatin (26 in total), please visit the HSDB records page.

---

Pharmacodynamics
Pitavastatin is an oral lipid-lowering drug that inhibits HMG-CoA reductase. It is used to lower plasma concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), while increasing plasma concentrations of high-density lipoprotein cholesterol (HDL-C). High plasma concentrations of LDL-C, low HDL-C, and high TG are associated with an increased risk of atherosclerosis and cardiovascular disease. The ratio of total cholesterol to HDL-C is a strong predictor of coronary artery disease, and a high ratio is associated with a higher risk of disease. Elevated HDL-C levels are associated with a reduced cardiovascular risk. Rosuvastatin reduces the incidence and mortality of cardiovascular disease by lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and raising HDL-C levels. Elevated cholesterol levels, especially LDL levels, are a significant risk factor for cardiovascular disease (CVD). Multiple landmark studies have demonstrated that using statins to lower LDL levels significantly reduces the risk of CVD and all-cause mortality. Because statins can reduce all-cause mortality, including fatal and non-fatal CVD, and decrease the need for revascularization or angioplasty after myocardial infarction, they are considered a cost-effective CVD treatment option. Evidence suggests that even in low-risk individuals (with a 5-year risk of major vascular events <10%), statins can reduce the relative risk of major cardiovascular events (heart attack, stroke, coronary revascularization, and death from coronary artery disease) by 20%–22% per 1 mmol/L reduction in LDL-C levels, without significant side effects or risks. Skeletal Muscle Effects Pitavastatin may cause myopathy (muscle pain, tenderness, or weakness, with creatine kinase (CK) levels exceeding 10 times the upper limit of normal) and rhabdomyolysis (acute renal failure with or without myoglobinuria). Rarely, rhabdomyolysis has resulted in death following statin use, including pitavastatin. Predisposing factors for myopathy include advanced age (≥65 years), female sex, uncontrolled hypothyroidism, and renal impairment. In most cases, muscle symptoms and elevated CK levels resolve upon timely discontinuation of the drug. Because daily doses of pitavastatin exceeding 4 mg are associated with an increased risk of severe myopathy, the product information recommends a maximum daily dose of 4 mg once daily. The risk of myopathy may increase if concomitantly taken with interacting medications such as fenofibrate, niacin, gemfibrozil, and cyclosporine during pitavastatin treatment. There have been reports of myopathy, including rhabdomyolysis, occurring when HMG-CoA reductase inhibitors are used in combination with colchicine; therefore, caution should be exercised when prescribing these two drugs concurrently. Real-world data from observational studies indicate that 10-15% of statin users may experience muscle pain during treatment. Liver Dysfunction There have been reports of pitavastatin causing elevated serum transaminases. In most cases, this elevation is transient and returns to normal or improves with continued treatment or a short break from the drug. Post-marketing reports show rare cases of fatal and non-fatal liver failure in patients taking statins, including pitavastatin. Patients with heavy alcohol consumption and/or a history of liver disease may have an increased risk of liver injury. Elevated Glycated Hemoglobin (HbA1c) and Fasting Blood Glucose Levels There have been reports of statin use (including pitavastatin) leading to elevated HbA1c and fasting blood glucose levels. Lifestyle optimization, including regular exercise, maintaining a healthy weight, and choosing healthy foods, is recommended. An in vitro study found that atorvastatin, pravastatin, rosuvastatin, and pitavastatin had dose-dependent cytotoxic effects on human pancreatic β-cells, reducing cell viability by 32%, 41%, 34%, and 29%, respectively, compared to the control group. Furthermore, insulin secretion rates decreased by 34%, 30%, 27%, and 19%, respectively, compared to the control group.

C25H24FNO4

421.46

421.168

147511-69-1

Pitavastatin Calcium;147526-32-7;Pitavastatin-d4;2070009-71-9;Pitavastatin-d5 sodium;Pitavastatin sodium;574705-92-3

5282452

White to off-white solid powder

1.4±0.1 g/cm3

692.0±55.0 °C at 760 mmHg

372.3±31.5 °C

0.0±2.3 mmHg at 25°C

1.680

3.45

3

6

8

31

631

2

C1CC1C2=NC3=CC=CC=C3C(=C2/C=C/[C@H](C[C@H](CC(=O)O)O)O)C4=CC=C(C=C4)F

VGYFMXBACGZSIL-MCBHFWOFSA-N

InChI=1S/C25H24FNO4/c26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31/h1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31)/b12-11+/t18-,19-/m1/s1

(E,3R,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

DMSO : ~100 mg/mL (~237.27 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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