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Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent FLC resistance and the perpetuation of fungal infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as a promising adjuvant for enhancing the fungicidal activity of FLC from a comprehensive library of 2372 FDA-approved drugs. PIT could render FLC fungicidal even at concentrations as low as 1 μM. The median lethal dose (LD50) of PIT was determined to be 103.6 mg/kg. We have discovered that PIT achieves its synergistic effect by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, and disrupting Golgi function. We employed a Candida albicans strain that demonstrated a notable tolerance to FLC to infect mice and found that PIT effectively augmented the antifungal efficacy of FLC against IFIs. This study is an illustrative example of how FDA-approved drugs can effectively eliminate fungal tolerance to FLC. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy of pitavastatin calcium and atorvastatin calcium on coronary atherosclerosis (CA) and compare the influence of the two schemes on adverse cardiovascular events. Methods: The medical records of 198 patients with CA admitted at Affiliated Hospital of Jiangsu University, China from August 2019 to May 2011 were analyzed retrospectively. The patients were grouped into pitavastatin calcium group (n = 102) and atorvastatin calcium group (n = 96). The efficacy, incidence of adverse cardiovascular events, as well as changes in blood lipid metabolism and blood glucose metabolism indices before and after therapy were recorded and compared. Results: Compared with atorvastatin calcium group, pitavastatin calcium group yielded a significantly higher overall response rate (ORR, p < 0.05) and presented a significantly lower total incidence of cardiovascular adverse events (p < 0.05). After therapy, pitavastatin calcium group displayed significantly lower triglyceride, total cholesterol and low-density lipoprotein-cholesterol levels (p < 0.05), and also presented significantly higher high-density lipoprotein-cholesterol levels (p < 0.05) in contrast to atorvastatin calcium group. Furthermore, pitavastatin calcium group presented significantly lower fasting blood glucose and glycosylated hemoglobin levels than atorvastatin calcium group (p < 0.05). Conclusion: Compared with atorvastatin calcium, pitavastatin calcium displays a better therapeutic effect in patients with CA, lowers the incidence of adverse cardiovascular events and improves glucose and lipid metabolism of patients. Future studies will focus on longer follow-up sessions to better understand the impact of the drugs on patient's prognosis. [ABSTRACT FROM AUTHOR]

HDL particles vary in lipidome and proteome, which dictate their individual physicochemical properties, metabolism, and biological activities. HDL dysmetabolism in nondiabetic hypertriglyceridemia (HTG) involves subnormal HDL-cholesterol and apoAI levels. Metabolic anomalies may impact the qualitative features of both the HDL lipidome and proteome. Whether particle content of bioactive lipids and proteins may differentiate HDL subclasses (HDL2b, 2a, 3a, 3b, and 3c) in HTG is unknown. Moreover, little is known of the effect of statin treatment on the proteolipidome of hypertriglyceridemic HDL and its subclasses. Nondiabetic, obese, HTG males (n = 12) received pitavastatin calcium (4 mg/day) for 180 days in a single-phase, unblinded study. ApoB-containing lipoproteins were normalized poststatin. Individual proteolipidomes of density-defined HDL subclasses were characterized prestatin and poststatin. At baseline, dense HDL3c was distinguished by marked protein diversity and peak abundance of surface lysophospholipids, amphipathic diacylglycerol and dihydroceramide, and core cholesteryl ester and triacylglycerol, (normalized to mol phosphatidylcholine), whereas light HDL2b showed peak abundance of free cholesterol, sphingomyelin, glycosphingolipids (monohexosylceramide, dihexosylceramide, trihexosylceramide, and anionic GM3), thereby arguing for differential lipid transport and metabolism between subclasses. Poststatin, bioactive lysophospholipid (lysophosphatidylcholine, lysoalkylphosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylinositol) cargo was preferentially depleted in HDL3c. By contrast, baseline lipidomic profiles of ceramide, dihydroceramide and related glycosphingolipids, and GM3/phosphatidylcholine were maintained across particle subclasses. All subclasses were depleted in triacylglycerol and diacylglycerol/phosphatidylcholine. The abundance of apolipoproteins CI, CII, CIV, and M diminished in the HDL proteome. Statin treatment principally impacts metabolic remodeling of the abnormal lipidome of HDL particle subclasses in nondiabetic HTG, with lesser effects on the proteome.

This study compared the difference between safflower yellow combined with pitavastatin calcium or with atorvastatin in preventing carotid plaque formation in cerebral infarction patients. Patients with acute cerebral infarction were randomized into groups A and B. Group A received safflower yellow and atorvastatin, while Group B received safflower yellow and pitavastatin calcium for 15 days. Both groups were evaluated for the efficacy of treatment after 6 months. Compared to the group receiving pitavastatin calcium, the atorvastatin group had lower serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, and inflammatory factors, and a higher high-density lipoprotein cholesterol level (P < 0.05). There was no difference in the effect of treatment on other markers such as whole blood viscosity, fibrinogen, and National Institutes of Health Stroke Scale scores (P > 0.05). However, the incidence of adverse reactions was higher in group A than in group B (P < 0.05). To sum up, safflower yellow combined with pitavastatin calcium for cerebral infarction patients can effectively reduce carotid plaque area and improve lipid levels, inflammation, and hemorheology. [ABSTRACT FROM AUTHOR]

Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent FLC resistance and the perpetuation of fungal infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as a promising adjuvant for enhancing the fungicidal activity of FLC from a comprehensive library of 2372 FDA-approved drugs. PIT could render FLC fungicidal even at concentrations as low as 1 μM. The median lethal dose (LD50) of PIT was determined to be 103.6 mg/kg. We have discovered that PIT achieves its synergistic effect by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, and disrupting Golgi function. We employed a Candida albicans strain that demonstrated a notable tolerance to FLC to infect mice and found that PIT effectively augmented the antifungal efficacy of FLC against IFIs. This study is an illustrative example of how FDA-approved drugs can effectively eliminate fungal tolerance to FLC.

BackgroundPatterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.MethodsThe REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.ResultsA total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.ConclusionsThere were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.Clinical trials registrationNCT02344290.

Purpose: The objective of the present study was to develop HP-β-cyclodextrin inclusion complex-based rapid orally disintegrating tablets of pitavastatin calcium by unique sublimation technique for enhancing solubility and dissolution profile of anti-lipidemic class II drug. Methods: The inclusion complex was prepared by a physical mixing method containing HP-β-cyclodextrin and pitavastatin calcium. The inclusion complex formation between the guest and host was confirmed by molecular docking studies. The developed inclusion complex was further characterized using differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffraction study (PXRD), and scanning electron microscopy studies. Fast orally disintegrating tablets of pitavastatin calcium inclusion complex were developed by a unique sublimation technique employing full factorial design (24) using the Design Expert® software. Independent factors, namely, type of super disintegrants and sublimating agents at varying concentrations, were studied for effect on disintegration time, hardness of the tablet, and in vitro drug release. Results: Molecular docking studies showed a score of −8.08. Optimized formulation containing 5% Ac-di-sol, 10% camphor showed hardness of about 3.37 ± 0.11 kg/cm2, least disintegration time 15.31 ± 0.32 s, and highest in vitro drug release of 99.11 ± 0.23% at the end of 15 min. Conclusion: The employed complexation method enhanced solubility and increased in vitro dissolution of pitavastatin calcium. It was concluded that fast orally disintegrating tablets containing inclusion complex gave desired characteristics which provided rapid onset of action by fast disintegration and could improve patient compliance. [ABSTRACT FROM AUTHOR]

Mahmoud H Teaima,1 Khaled M Abdel-Haleem,2 Rewan Osama,2 Mohamed A El-Nabarawi,1 Osama S Elnahas2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza, EgyptCorrespondence: Mahmoud H TeaimaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, EgyptTel +201005840264Email mahmoud.teaima@pharma.cu.edu.egSignificance: Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy.Purpose: This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon® and Lornoxicam®).Methods: Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q10 min. LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma.Results: Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst® (F2) had significantly (p< 0.05) the fastest DT (6.66± 1.52 s) and highest Q10 min (79.07± 2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products.Conclusion: The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.Keywords: oral disintegrating tablets, co-processed excipients, pitavastatin calcium, Lornoxicam, in-vivo pharmacokinetic study, liquid chromatography-mass spectrometry

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a)

HDL particles vary in lipidome and proteome, which dictate their individual physicochemical properties, metabolism, and biological activities. HDL dysmetabolism in nondiabetic hypertriglyceridemia (HTG) involves subnormal HDL-cholesterol and apoAI levels. Metabolic anomalies may impact the qualitative features of both the HDL lipidome and proteome. Whether particle content of bioactive lipids and proteins may differentiate HDL subclasses (HDL2b, 2a, 3a, 3b, and 3c) in HTG is unknown. Moreover, little is known of the effect of statin treatment on the proteolipidome of hypertriglyceridemic HDL and its subclasses. Nondiabetic, obese, HTG males (n = 12) received pitavastatin calcium (4 mg/day) for 180 days in a single-phase, unblinded study. ApoB-containing lipoproteins were normalized poststatin. Individual proteolipidomes of density-defined HDL subclasses were characterized prestatin and poststatin. At baseline, dense HDL3c was distinguished by marked protein diversity and peak abundance of surface lysophospholipids, amphipathic diacylglycerol and dihydroceramide, and core cholesteryl ester and triacylglycerol, (normalized to mol phosphatidylcholine), whereas light HDL2b showed peak abundance of free cholesterol, sphingomyelin, glycosphingolipids (monohexosylceramide, dihexosylceramide, trihexosylceramide, and anionic GM3), thereby arguing for differential lipid transport and metabolism between subclasses. Poststatin, bioactive lysophospholipid (lysophosphatidylcholine, lysoalkylphosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylinositol) cargo was preferentially depleted in HDL3c. By contrast, baseline lipidomic profiles of ceramide, dihydroceramide and related glycosphingolipids, and GM3/phosphatidylcholine were maintained across particle subclasses. All subclasses were depleted in triacylglycerol and diacylglycerol/phosphatidylcholine. The abundance of apolipoproteins CI, CII, CIV, and M diminished in the HDL proteome. Statin treatment principally impacts metabolic remodeling of the abnormal lipidome of HDL particle subclasses in nondiabetic HTG, with lesser effects on the proteome., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

To comparison the efficacy and safety of pivastatin calcium and atorvastatin calcium in the Treatment of Coronary Heart Disease. 100 patients with coronary heart disease from March 2016 to December 2018 were divided into the pitavastatin calcium group(n=50) and the atorvastatin calcium group (n=50). The blood glucose(Glu), Glycated hemoglobin(HbA1c), Ultra- sensitive C reaction protein (hsCRP), Total cholesterol (TC), Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol(HDL-C), Acetyltransferase(ALT), Valley grass transaminase(AST), Creatinine(Cr), Creatine kinase (CK)were monitored and compared before treatment and after treatment of 6,12 months. After 6months and 12months treatment the pitavastatin calcium group HDL-C were significantly elevated (P<0.05), hsCRP were significantly lower(P<0.05). After 6months and 12months the atorvastatin calcium group HDL-C and hsCRP compared to before treatment the difference were not statistically(P>0.05). The atorvastatin calcium group HbA1c were elevated after 12months treatment with statistically differences(P<0.05), but the pitavastatin calcium were not elevated(P>0.05). The two groups TC, LDL-C were lower with statistically significant differences(P<0.05). The differences between Glu, ALT, AST, Cr, CK before treatment and after treatment were without statistically differences (P>0.05), 1patient was removed because of transaminase elevated. Both pitavastatin calcium and atorvastatincalcium can lower LDL-C, TC、TG in Coronary Heart Disease patients, Moreover, the pitavastatin calcium can elevate HDL-C level and lower hsCRP level. Meanwhile, the pitavastatin calcium had no evidence in new diabetes, it was efficacy and safety in long-term treatment. [ABSTRACT FROM AUTHOR]

An isocratic stability-indicating reverse phase high performance liquid chromatographic diode array detection method has been developed and validated for the quantitative determination of pitavastatin calcium in the presence of its degradation products. The chromatographic separation was achieved on Phenomenex Luna C18 column (250 X 4.0 mm id, 5μm) in the isocratic mode using acetonitrilemethanol-water (35:25:40, v/v/v, pH 3 adjusted with orthophosphoric acid) as mobile phase. The drug is subjected to different accelerated stress conditions and peaks of the degradation products were well resolved from the pure drug, which indicates the specificity and stability-indicating properties of the method. The method was linear (r= 0.9998) over the concentration range of 5-30 μg/mL. The proposed method was used to investigate the degradation kinetics of PTV in acidic condition at different temperatures. Degradation of pitavastatin followed first-order kinetics, and rate constant (k), half life (t1/2), time left for 90% potency (t90) and energy of activation were calculated. [ABSTRACT FROM AUTHOR]

A simple reverse-phase method for the selective quantification of pitavastatin calcium (PIT) and its related substances was developed. The method demonstrated an excellent separation between PIT and each of 15 impurities (including its isomers and degradants) within a short run time of 12 min by HPLC. A rapid resolution similar to that of UHPLC was achieved using high flow rate on superficially porous C18 stationary phase. A synergistic combination of quality by design approach and use of a superficially porous column delivered a HPLC method with ultra-high performance. Forced degradation studies proved the method to be highly specific (mass balance > 98 %) and the structures of major degradation products were proposed based on LC-MS analysis. The results of validation proved the method to be highly precise (%RSD < 4), accurate (recoveries in range of 100 ± 7 %), linear ( r > 0.999) and sensitive (LOQ ≤ 0.02 % and LOD ≤ 0.005 %) for all the impurities and drug. Use of multivariate analysis helped to incorporate high robustness in the method. The method is valuable for quantification of PIT and its related substances in both drug substance and oral solid dosage form. [ABSTRACT FROM AUTHOR]

A novel approach to synthesize pitavastatin calcium ( 1 ), an effective HMG-CoA reductase inhibitor, based on readily available and attractively functionalized ( R )-3-chloro-1,2-propanediol is reported. This work highlights an intermolecular diastereoselective bromine-induced cyclization of homoallylic carbonate to meet stereochemical challenges in the synthesis of statins. An efficient route to a new triphenylphosphonium tetrafluoroborate salt of a quinoline core is also presented. [ABSTRACT FROM AUTHOR]

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Background: Pitavastatin, a fully synthetic β-hydroxy- β-methylglutaryl-coenzyme A reductase inhibitor, is potent for the treatment of primary hyperlipidemia and mixed dyslipidemia. Recently, the original product and some generic products of pitavastatin calcium have become available in China. However, the intrasubject variability and interchangeability of this newly developed generic product and the branded innovator product have rarely been investigated in the Chinese population. Purpose: The aim of this study is to develop and compare the scaled-average, population, and individual bioequivalence (BE) of pitavastatin calcium tablets in healthy Chinese volunteers. This study will be used to allow for the interchangeability (switchability and prescribability) of the 2 products in clinical medication in China. Methods: A single-dose, reference-replicated, 3-period crossover BE study was conducted in 36 healthy male volunteers. Plasma samples were collected before and after oral administration of 2-mg test or reference tablets. A LC-MS/MS method was used to determine the concentration of pitavastatin calcium. A noncompartmental method was used to investigate the pharmacokinetic parameters. The ANOVA and 90% CIs of ln(AUC0-t) and ln(Cmax) were used for statistical analysis of scaled-average BE. A nonparametric test (Wilcoxon signed rank test) was performed to Tmax. The analyses of population BE and individual BE were used to assess the switchability and prescribability of the 2 products.Findings: Thirty-six volunteers were enrolled in this clinical research; 33 volunteers completed the 3 treatment periods. The mean (SD) relative bioavailability calculated from the ratios (T/R) of AUC0-t was 101.3% (19.7%). The mean ln(AUC0-t) and ln(Cmax) were 98.64 (90% CI, 93.44-104.13) and 98.68 (90% CI, 91.88-105.99) within previously stipulated ranges recommended by the US Food and Drug Administration and the China Food and Drug Administration (CFDA). The intrasubject %CVs of AUC0-t and Cmax were 12.0% and 18.0% for the reference tablet and 13.0% and 17.0% for the test tablet. No significant differences were found among Tmax (0.742 ± 0.276, 0.674 ± 0.202, and 0.689 ± 0.226, respectively) for reference tablet 1, reference Supplemental Table II in the online version at http://dx.doi.org/10.1016/j. clinthera.2014.06.21, and test tablet by a Wilcoxon test (P 4 0.05). For ln(AUC0-t) and ln(Cmax), the statistical test-reference ratios were 99.13% and 98.95%, respectively. After inspecting the results for reference and mixed scaling, all the upper confidence limits were o0; therefore, population and individual BE were given. Implications: In the healthy Chinese males, the generic and branded name tablets of pitavastatin calcium are bioequivalent at the rate and extent of absorption after a comparison of scaled-average, population, and individual BE and thus may be used interchangeably. Both the formulations are generally well tolerated. [ABSTRACT FROM AUTHOR]

A new, simple, selective, and robust normal-phase method for the accurate quantification of all the four stereoisomers and one geometrical isomer of pitavastatin calcium (PIT) in drug substances and drug products was developed. The method is capable of quantifying all the isomers in the presence of other related substances. Separation was achieved using immobilized amylose stationary phase (Chiralpak IA) with a mixture of n-heptane, 1-butanol, methanol, formic acid, and diethylamine. Multivariate analysis and statistical tools were used to develop this highly robust method in a short span of time. A central composite design was employed to study the main effects and interactions of the independent variables. The method exhibited consistent, high-quality recoveries [97.3 ± 1.7 to 99.3 ± 2.1 (mean ± RSD)] with a high precision for all the isomers. Linear regression analysis revealed an excellent correlation between peak responses and concentrations ( r values of 0.9990-0.9998) for the isomers. The method is sensitive enough to quantify any isomers above 0.02 % and detect any isomer above 0.006 % in PIT. Forced degradation studies proved that the method is specific for isomers. m/ z values were determined for the major degradants and their possible structures were proposed on the basis of the known reactivity. [ABSTRACT FROM AUTHOR]

A simple, sensitive, reliable, and rapid HPTLC method has been developed for the determination of pitavastatin calcium in tablet dosage form. Identification and determination were performed on aluminum backed silica gel 60F254 washed with methanol. The mobile phase of ethyl acetate-methanol-ammonia-1 drop formic acid (7:2:0.8) calibration plots were established showing the dependence of response (peak area) on the amount chromatographed. The spot were scanned at 245 nm. The method has a linear range of 50-250 ng/spot. The method was validated for selectivity, repeatability, and accuracy. The method was used for determination of the compound in commercial pharmaceutical dosage forms. It is a more effective option than other chromatographic techniques in routine quality control. [ABSTRACT FROM AUTHOR]

Two simple, rapid, specific and accurate analytical methods for the estimation of cefetamet pivoxil hydrochloride and pitavastatin calcium in bulk drug and in their tablet formulations are described. These methods are based on difference spectrophotometry, wherein the measurement is done at maximum 221 nm and minimum 275 nm for cefetamet whereas at maximum 240 nm and minimum 259 nm for pitavastatin. The Beer's law was obeyed in the concentration range of 1-35 µg/ml and 1-25 µg/ml and the molar absorptivities were 1.3x104 lit mol-1cm-1 and 2.4x104 lit mol-1cm-1 for cefetamet pivoxil hydrochloride and pitavastatin calcium, respectively. The proposed methods were validated and successfully applied to the estimation of drugs in tablet formulations. [ABSTRACT FROM AUTHOR]

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a) <10 mg/dl] received pitavastatin calcium (4 mg/day) for 180 days in a single-phase unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids {LPC, lysophosphatidylinositol (LPI), lysoalkylphosphatidylcholine [LPC(O)]; 9, 0.2, and 0.14 mol per mole of apoB, respectively; all P < 0.001 vs. LDL1-4}, suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI, and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5-3 mol per mole of apoB; 3-7 mmol per mole of PC) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy., (Copyright © 2020 Chapman et al.)

Background: Pitavastatin, a fully synthetic β-hydroxy-β-methylglutaryl-coenzyme A reductase inhibitor, is potent for the treatment of primary hyperlipidemia and mixed dyslipidemia. Recently, the original product and some generic products of pitavastatin calcium have become available in China. However, the intrasubject variability and interchangeability of this newly developed generic product and the branded innovator product have rarely been investigated in the Chinese population., Purpose: The aim of this study is to develop and compare the scaled-average, population, and individual bioequivalence (BE) of pitavastatin calcium tablets in healthy Chinese volunteers. This study will be used to allow for the interchangeability (switchability and prescribability) of the 2 products in clinical medication in China., Methods: A single-dose, reference-replicated, 3-period crossover BE study was conducted in 36 healthy male volunteers. Plasma samples were collected before and after oral administration of 2-mg test or reference tablets. A LC-MS/MS method was used to determine the concentration of pitavastatin calcium. A noncompartmental method was used to investigate the pharmacokinetic parameters. The ANOVA and 90% CIs of ln(AUC0-t) and ln(Cmax) were used for statistical analysis of scaled-average BE. A nonparametric test (Wilcoxon signed rank test) was performed to Tmax. The analyses of population BE and individual BE were used to assess the switchability and prescribability of the 2 products., Findings: Thirty-six volunteers were enrolled in this clinical research; 33 volunteers completed the 3 treatment periods. The mean (SD) relative bioavailability calculated from the ratios (T/R) of AUC0-t was 101.3% (19.7%). The mean ln(AUC0-t) and ln(Cmax) were 98.64 (90% CI, 93.44-104.13) and 98.68 (90% CI, 91.88-105.99) within previously stipulated ranges recommended by the US Food and Drug Administration and the China Food and Drug Administration (CFDA). The intrasubject %CVs of AUC0-t and Cmax were 12.0% and 18.0% for the reference tablet and 13.0% and 17.0% for the test tablet. No significant differences were found among Tmax (0.742 ± 0.276, 0.674 ± 0.202, and 0.689 ± 0.226, respectively) for reference tablet 1, reference Supplemental Table II in the online version at 10.1016/j.clinthera.2014.06.21, and test tablet by a Wilcoxon test (P > 0.05). For ln(AUC0-t) and ln(Cmax), the statistical test-reference ratios were 99.13% and 98.95%, respectively. After inspecting the results for reference and mixed scaling, all the upper confidence limits were <0; therefore, population and individual BE were given., Implications: In the healthy Chinese males, the generic and branded name tablets of pitavastatin calcium are bioequivalent at the rate and extent of absorption after a comparison of scaled-average, population, and individual BE and thus may be used interchangeably. Both the formulations are generally well tolerated. Chinese Clinical Trial identifier: ChiCTR-TTRCC-13003973., (Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.)