Combination Of Atorvastatin Research Articles

Potency of atorvastatin in parasitemia clearance of plasmodium and the effects of the combination of atorvastatin and artemisinin derivatives on parasitemia clearance and organ toxicity

Abstract Objective: This study investigated the effects of atorvastatin and artemisinin based combination therapies (ACTs), administered individually and orally co-administered on some hepatotoxic biomarkers and

Význam fixních kombinací na poli kardiovaskulární prevence aneb možnost léčit dvě diagnózy jednou tabletou

In the care of a cardiovascular risk patient there is certainly a more frequent situation in which we try to influence several risk factors at the same time. Treatment of a single self-occurring risk factor is rather an exception. In most cases, we need to intervene with more risk factors, often involving combination therapy, which can achieve the desired goals more quickly and reliably. However, with the number of tablets taken by the patient, the patients willingness to take long-term and correct use decreases, which has a significant impact on the effectiveness of therapy and the development of individual cardiovascular risk. In an effort to control all risk factors for cardiovascular disease, there is a growing need to extend the availability of fixed drug formulations to suit the patients ease of use and suitably formulated with varying dose grades to meet the needs of our attending physicians. With regard to the fact that early intervention of risk factors brings greater benefits than deferred, we are looking for appropriate ways to manage it. The current intervention of arterial hypertension and dyslipidemia with safe and proven drugs seems to be one of the ways to further improve the results of the prevention of cardiovascular diseases. The new fixed combination of atorvastatin with perindopril, which is entering the Czech market right now, appears to be in many ways an ideal “tablet for cardiovascular prevention”.

53P - Phase II study of atorvastatin in combination with radiotherapy and temozolomide in patients with glioblastoma (ART): Final analysis report

BackgroundGlioblastoma is the one of most fast-growing primary brain tumor in adult and it carries the worst prognosis. Atorvastatin is an inhibitor of HMG-CoA reductase, a rate-limiting enzyme in the mevalonate pathway. Preclinical studies demonstrate encouraging anticancer activity of statins. The primary objective of the study was to evaluate the efficacy of Atorvastatin in addition to the standard therapy in patients with glioblastoma. MethodsIn this open-label, prospective, single-arm, phase II study, eligible patients received Atorvastatin in combination with standard therapy comprising radiotherapy and Temozolomide (TMZ). The primary endpoint is progression free survival (PFS) at 6 months. A minimum of 80% power required at least 32 eligible patients with planned final analysis after at least 1 year from last recruited patient. ResultsFrom January 2014 to December 2016, 36 evaluable patients were enrolled. Median age was 52 (20-69); 22% were ≥ 60 years of age and 62% were male. 97% of patients underwent resection. All patients have received Atorvastatin for a median of 6.2 (0.3 – 28 ) months duration, 80% of patients have discontinued this because of disease progression. At a median follow-up of 19 months, PFS-6 rate was 66% with median PFS of 7.6 months. Median overall survival was 19.9 months (4.8 – 42.5 months). Grades 3 and 4 hematological adverse events, including neutropenia and thrombocytopenia occurred in 7% and 12 % of patients respectively. On multivariate analysis, worse survival was associated in patients with baseline high LDL level (p = 0.046) and better survival was seen in patients received adjuvant TMZ (p = 0.001) and methylated tumors (p = 0.013). ConclusionsThis study did not meet its primary endpoint of PFS-6 compared to historical controls. However, this study proves the fact that high LDL level was found to be an important independent predictor of poor cancer-related outcome. Future clinical trials testing statins should aim to enroll patients with slow-growing tumors. Clinical trial identificationclinical trial information: NCT02029573. Legal entity responsible for the studyKing Fahad Medical City. FundingKing Fahad Medical City. DisclosureAll authors have declared no conflicts of interest.

Exploration of biologic significances and mechanisms of combined atorvastatin with PI3K/Akt inhibitor in radiotherapy of colorectal cancer

Abstract Background Radiotherapy of pelvic or abdominal cancer may cause radiation enteritis or colitis. We have reported previously that atorvastatin which is a cholesterol-lowering drug and attenuate radiation-induced intestine damage including apoptosis, inflammatory, fibrogenesis and oxidative stress through activation of autophagy. Several studies have been demonstrated that statin drugs have effects of inhibiting of tumor cell proliferation. We sought to explore whether atorvastatin can play a role in enhancing the efficiency of radiotherapy combined with BKM120 and decreasing radiation-induced colitis. Methods Two colorectal cancer cell lines including HCT116, HT29, and HCT116 xenograft tumors were separated into 3 study groups: (1) untreated, (2) NVP-BKM120 + RT (CCRT), (3) the administration of atorvastatin followed by CCRT. MTT and colony assay was used to determine whether the administration of atorvastatin can increase sensitivity of colorectal cancer cell to CCRT. Moreover, activation of apoptosis (the levels of cleaved-caspase 3), inflammation (the levels of NF-κB p65), and AKT/mTOR signaling pathway was analyzed to clarify the radiosensitizing mechanism induced by atorvastatin. In the HCT116 xenograft tumor model, tumor sizes and body weights of the mice were measured once per week after treatment for evaluation of anti-tumor effect. Results In MTT assay and colony formation assay, we observed that the administration of atorvastatin followed by CCRT significantly inhibits cell viability in 2 CRC cells when compared with concurrent BKM120 and RT treatment. Moreover, atorvastatin could significantly sensitize colorectal cancer cell lines to the CCRT by upregulated the level of apoptosis and attenuating CCRT-induced inflammation and AKT/mTOR signaling. Furthermore, the animal experiments also showed similar results that the administration of atorvastatin could significantly increase anti-tumor effect induced by CCRT. Conclusions Our data indicated that atorvastatin treatment could attenuate intestinal damage and sensitize colorectal cancer to CCRT. This approach will help us further develop a more efficient modality therapy for patients with colorectal cancer. Legal entity responsible for the study National Taiwan University Hospital. Funding Has not received any funding. Disclosure The author has declared no conflicts of interest.

The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis.

Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3105 participants were included in the final analysis; 1558 (50.18%) participants received ezetimibe and statin combination therapy and 1547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients coadministered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (p < 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.

Exploring Therapeutic Potential of Atorvastatin Against Gram-positive and Gram-negative Bacteria: In silico, In vitro and In vivo Evidences.

The incidences of opportunistic bacterial infections have increased in the past two decades or is expected to increase in the near future. Despite the availability of various classes of antibiotics, bacterial infections are not handled properly. Thus, in the present study, we have repurposed atorvastatin against various types of bacterial strains by using in silico, in vitro, and in vivo studies. Furthermore, a preliminary safety study was conducted using MTT assay. In silico study results have revealed that atorvastatin has good interaction with various targets of bacterial cell like that of the reference ligand. However, under in vitro conditions,it was found that atorvastatin was effective at higher concentrations (>128 μg/ml) against various bacterial strains. Thus, further, atorvastatin was tested in combination with standard antibiotics and has shown a synergistic effect. The MTT assay results have revealed non-cytotoxic activity of atorvastatin. In conclusion, atorvastatin in combination with standard drugs could be developed as an antibacterial agent.

Isolation, Identification and Characterization of Degradation Impurity of Atorvastatin in Fixed Dose Combination of Atorvastatin and Ezetimibe

The objective of this study is to isolation and characterization of unknown degradation product of Atorvastatin calcium in combination formulation product with Ezetimibe by using modern techniques of separation and aracterization. An unknown impurity is generating during a forced degradation study of Atorvastatin and Ezetimibe fixed-dose combination tablets. By using the gradient reversed-phase high-pressure liquid chromatographic method, unknown degradation impurity was detected and quantified in the range of 0.05% to 0.2% of Atorvastatin. The impurity was enriched by extreme oxidation degradation of Atorvastatin and isolated through preparative HPLC. The structure of the impurity was characterized by mass and NMR spectrum.

Does the use of high dose atorvastatin in combination with dual antiplatelet therapy modify residual platelet activity in patients with acute coronary syndrome?

Does the use of high dose atorvastatin in combination with dual antiplatelet therapy modify residual platelet activity in patients with acute coronary syndrome?

Effectiveness of Echinochrome on HFD-Induced Hyperlipidemia in Rats

Obesity has been identified with an expanded danger of a progression of illnesses that include different organ-frameworks of the body. In the present examination, we evaluated the hypolipidemic properties of Echinochrome (Ech) pigment in a high-fat diet (HFD) induced hyperlipidemia in rats. After the hyperlipidemic model was set up, rats were haphazardly separated into five groups as follows: normal control group, HFD group, Atorvastatin (ATOR) group (80 mg/kg), Ech group (1 mg/kg) and combined group ATOR + Ech. The outcomes demonstrated that Ech improves lipid profile, liver functions, kidney functions and antioxidant markers of obese rats. The findings of the present investigation indicated that the Ech possesses hypolipidemic potential in obese rats.

Atorvastatin in combination with conventional antimicrobial treatment of Helicobacter pylori eradication: A randomized controlled clinical trial.

Helicobacter pylori is one of the main causes of digestive diseases, which is difficult to treat and requires the administration of several antimicrobial agents. Considering the anti-inflammatory and antibacterial effect of atorvastatin, the present study aimed at adding this agent to a four-drug regimen in order to eradicate H.pylori. A total of 220 patients with H.pylori infection were included in the current randomized controlled clinical trial. In the current study, 110 patients in the control group received a 14-day regimen of amoxicillin, clarithromycin, bismuth, and esomeprazole, and 110 patients in the intervention group received 40mg of atorvastatin daily plus the antibiotic regimen for 14weeks. The treatment results were evaluated 1month later using H.pylori stool antigen test. Data were collected using checklist and analyzed using chi-squared and Fisher's exact tests with spss version 18. Helicobacter pylori eradication rate in the intervention and control groups was 78.18% and 65.45%, respectively (P=0.025), and there was a significant difference in terms of non-ulcer dyspepsia between the groups (P=0.049), but there was no significant difference in age, gender, and body mass index between the two groups (P<0.05). The present study results showed that adding atorvastatin to the four-drug regimen of omeprazole, clarithromycin, bismuth, and amoxicillin is effective in the eradication of H.pylori. Also, the addition of atorvastatin to H.pylori eradication therapy is more effective in patients with non-ulcer dyspepsia.

Combination of atorvastatin and fenofibrate altered androgenic activities of male rats

Background and objective: Many drugs and chemical substances may induce sexual dysfunction and have a negative impact on male fertility. Lipid-lowering agents like statins and fibrates are usually recommended for cardiovascular diseases prevention. However, the combination of atorvastatin and fenofibrate is the subject of questions concerning their effect on androgenic activities in this study. This study was designed to evaluate the efficacy and toxicity of atorvastatin, fenofibrate, and their combination on sperm parameters, sexual hormones, and histopathology of the testis. Methods: Twenty-four male rats were divided into four groups, each of six. The first group served as a control. The second, third, and fourth groups received atorvastatin, fenofibrate, and their combination, respectively. After 28 days, blood samples were collected for hormones and other parameters evaluations. Testis and epididymis were taken for histopathology studies and sperm parameters assessments. Results: Fenofibrate showed a significant reduction in sperm viability and serum levels of luteinizing and estradiol hormones. The combination of both drugs significantly reduced the sperm count and viability in normal male rats. Both atorvastatin and its combination mildly changed the histological structures of the testis, reduced number of spermatozoa, and arrested spermatogenesis. Conclusion: The findings from this prospective study suggested that there was no harmful effect of atorvastatin usage on conventional sperm parameters and sexual hormones. Fenofibrate usage was not adversely associated with sperm parameters other than sperm viability. The combination of atorvastatin and fenofibrate significantly reduced the sperm count and viability. No deleterious effects of the drugs were seen on the testosterone, which was the essential hormone for all stages of spermatogenesis, sperm production, maturation, and transport.

Efficacy of Atorvastatin Plus Pegylated Interferon and Ribavirin Versus Pegylated Interferon and Ribavirin Alone in Chronic Hepatitis C Patients with Genotype-3a

Chronic hepatitis C infection has created a huge burden of disease causing serious healtheffects. The combination therapy used to treat hepatitis C virus (HCV) infection includes Pegylatedinterferon and Ribavirin. As cholesterol biosynthesis plays a pivotal role in HCV replication, the use ofvarious statins has been associated with higher sustained viral response Objective: To compare theefficacy of atorvastatin plus pegylated interferon and ribavirin versus pegylated interferon and ribavirinalone in patients of chronic hepatitis C with genotype-3a Methods: This Randomized controlled trial wasconducted at outpatient department, Mayo Hospital Lahore for six months i.e. May to November 2017.After ethical approval, 60 patients of ages 25 to 55 years of either gender with chronic hepatitis C withgenotype 3a were included in the study. Informed consent was taken from all patients. Then patients wererandomly allocated into two groups “A” and “B” using random number table. Patients in Group A receivedstandard of care treatment for chronic hepatitis C i.e. pegylated interferon and ribavirin while the patientsin Group B also received tab atorvastatin along with the standard treatment. Patients were follow up for 4week. Blood samples were collected and HCV RNA detection. All this information were entered inproforma Results: In standard therapy group, the mean age of patients was 39.50±8.39years. Inatorvastatin plus standard therapy group, the mean age of patients was 34.30±6.78years. In standardtherapy group, there were 25 (83.3%) males and 5 (16.7%) females. In atorvastatin plus standard therapygroup, there were 16 (53.3%) males and 14 (46.7%) females. After 4 weeks, Rapid Virological Response(RVR) was achieved in 4 (13.3%) patients in standard therapy group while in 14 (46.7%) in atorvastatin plusstandard therapy group. The difference was significant (p&lt;0.05) Conclusions: Atorvastatin incombination with Pegylated interferon and ribavirin have better efficacy as compared to Pegylatedinterferon &amp; ribavirin alone in chronic hepatitis C-3a.

Concomitant administration of atorvastatin with N-acetylcysteine mitigates liver injury and steatosis in experimental non-alcoholic fatty liver disease

Although numerous efforts have been directed towards searching for new treatments against non-alcoholic fatty liver disease (NAFLD), there are no approved pharmacologic agents up to date. This study evaluates the therapeutic effect of concomitant administration of atorvastatin (ATO) and N-Acetylcysteine (NAC) with/without diet control. Nine groups of rats were divided into; normal, rats fed on high-fat diet for 12 weeks (NAFLD-HFD model), HFD-rats switched to regular diet (NAFLD-RD model), NAFLD-HFD or -RD rats treated with either ATO or NAC orally with 30 or 500 mg/kg/day respectively or both for 8 weeks. NAFLD-HFD rats exhibited remarkable steatosis with lobular inflammation, hepatocytes vacuolation and fibrosis, as well as significant changes in lipid profile, oxidative stress and adipocytokines and these manifestations were less prominent in the HFD-RD group. ATO and NAC combination with diet control has the added benefits on ameliorating lipid levels, liver enzymes, oxidative stress, hepatic steatosis (9.01% ± 1.66% vs 13.21% ± 2.20% for ATO and 25.60% ± 2.11% for NAC), inflammation, hepatocyte vacuolation and fibrosis versus each drug separately. Conclusion; ATO and NAC concomitant therapy has a greater effect on NAFLD as compared to monotherapy and is recommended for further investigation in clinical trials.

Effects and mechanism of inhibition of naringin in combination with atorvastatin on prostate cancer cells in vitro and in vivo

Background/aimNaringin, a naturally occurring flavanone glycoside, can inhibit oxidative stress and inflammatory reactions. Atorvastatin, which belongs to the class of drugs called statins, is an inhibitor of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase and it has shown anticancer activity in prostate cancer (PCa). The present study investigated whether the combination of atorvastatin and naringin has an effect on inhibiting growth in PCa and the mechanisms underlying this effect. MethodsCell growth was assessed by CCK-8 and trypan blue exclusion assay, and the IC50 of LNCaP and PC-3 cells were determined by MTT assay. Scratch migration and matrigel-coated transwell invasion were used to assess both migration and invasion in prostate cancer cell lines. The expression levels of p-Akt, p-STAT3, survivin, AR, Bcl-2, and Bax in prostate cancer cell lines were determined by Western blot. PC-3 and LNCaP xenografts were applied to assess the effect in vivo. ResultsNaringin in combination with atorvastatin had a synergistic inhibitory effect on growth in the prostate cancer cell lines PC-3 and LNCaP, and the combination more strongly inhibited migration and invasion than either single drug. The combination of atorvastatin with naringin potently inhibited the expression levels of AR, p-Akt, survivin, p-STAT3, and Bcl-2. However, an increase in the level of p-STAT3 was found in the PC-3 cells treated with atorvastatin and naringin alone, which differed from that observed in LNCaP. Moreover, the level of Bax in the prostate cancer cell lines treated with atorvastatin and naringin was higher than in those treated with either drug alone. Atorvastatin or naringin treatment had an inhibitory effect on the growth of PC-3 and LNCaP tumors in vivo, and this was especially true of the combined treatment. ConclusionsThe data suggest that the combination of atorvastatin and naringin may be an effective method for inhibiting the growth of prostate cancer. Further research is needed to determine the mechanism of action of the combination of atorvastatin and naringin.

Optimization of Timing and Times for Administration of Atorvastatin-Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction.

Our previous studies showed that the combination of atorvastatin (ATV) and single injection of ATV‐pretreated mesenchymal stem cells (MSCs) (ATV‐MSCs) at 1 week post‐acute myocardial infarction (AMI) promoted MSC recruitment and survival. This study aimed to investigate whether the combinatorial therapy of intensive ATV with multiple injections of ATV‐MSCs has greater efficacy at different stages to better define the optimal strategy for MSC therapy in AMI. In order to determine the optimal time window for MSC treatment, we first assessed stromal cell‐derived factor‐1 (SDF‐1) dynamic expression and inflammation. Next, we compared MSC recruitment and differentiation, cardiac function, infarct size, and angiogenesis among animal groups with single, dual, and triple injections of ATV‐MSCs at early (Early1, Early2, Early3), mid‐term (Mid1, Mid2, Mid3), and late (Late1, Late2, Late3) stages. Compared with AMI control, intensive ATV significantly augmented SDF‐1 expression 1.5∼2.6‐fold in peri‐infarcted region with inhibited inflammation. ATV‐MSCs implantation with ATV administration further enhanced MSC recruitment rate by 3.9%∼24.0%, improved left ventricular ejection fraction (LVEF) by 2.0%∼16.2%, and reduced infarct size in all groups 6 weeks post‐AMI with most prominent improvement in mid groups and still effective in late groups. Mechanistically, ATV‐MSCs remarkably suppressed inflammation and apoptosis while increasing angiogenesis. Furthermore, triple injections of ATV‐MSCs were much more effective than single administration during early and mid‐term stages of AMI with the best effects in Mid3 group. We conclude that the optimal strategy is multiple injections of ATV‐MSCs combined with intensive ATV administration at mid‐term stage of AMI. The translational potential of this strategy is clinically promising. stem cells translational medicine 2019;8:1068–1083

Treatment of Hypertensive and Hypercholesterolaemic Patients with the Triple Fixed Combination of Atorvastatin, Perindopril and Amlodipine: The Results of the CORAL Study.

Hypertension and hypercholesterolaemia are important contributors to the development and progression of atherosclerosis. The coexistence of these two conditions is rather common: hypercholesterolaemia is present in 40-60% of hypertensive patients. Remarkably, patient compliance with antihypertensive regimens is better than with statin therapy. Thus, the inclusion of statins and blood pressure-lowering agents into a fixed combination might even double the effectiveness of statin therapy, and thereby achieve significantly greater reduction of cardiovascular risk. The CORAL study was a 3-month, prospective, multicentre, observational, non-interventional survey, which evaluated the blood pressure- and lipid-lowering efficacy of the triple fixed combination of atorvastatin/perindopril/amlodipine, administered in various dose combinations. The efficacy of the triple fixed combination was reflected by the changes of the blood pressure readings taken in the office and during 24-h blood pressure monitoring (3months elapsed between visits1 and 3). The laboratory parameters obtained during data acquisition were also recorded. After 3months of therapy, mean office blood pressure decreased from 158.5 ± 16.7/91.7 ± 9.4 to 132.2 ± 8.3/80.1 ± 6.8mmHg (p < 0.0001), whereas mean 24-h blood pressure decreased from 146.0 ± 14.5/82.5 ± 12.1 to 132.1 ± 13.2/75.6 ± 9.9mmHg. With regard to metabolic parameters, the inclusion of pre-existing statin therapy in the fixed combination led to further, significant reduction of lipid parameters as follows: total cholesterol level from 6.18 ± 1.15 to 5.16 ± 0.88mmol/L, LDL-cholesterol from 3.41 ± 1.01 to 2.80 ± 0.82mmol/L and triglyceride level from 2.26 ± 1.17 to 1.82 ± 0.83mmol/L (all p < 0.0001). Treatment with the fixed triple combination of atorvastatin, perindopril and amlodipine might take us closer to the optimal therapy for hypertensive patients with hypercholesterolaemia. The expected improvement of patient adherence to treatment may result in an increase of the percentage patients who achieve both blood pressure control and the LDL-cholesterol targets recommended in guidelines. Moreover, this may translate into the further decline of the risk of prospective cardiovascular events. Egis Pharmaceuticals.

Atorvastatin in Combination with Pegylated Interferon and Ribavirin Provided High Rate of Sustained Virological Response in Patients with Genotype 3 Hepatitis C Virus

BACKGROUND:Chronic hepatitis C virus infection represents a more frequent cause of liver cirrhosis and hepatocellular carcinoma. Statins, inhibit HCV replication in vitro, enhance the antiviral effect of the already known antiviral drugs and reduce their resistance.AIM:To determine the impact of additional therapy (treatment with Atorvastatin 20 mg) to the standard antiviral therapy (pegylated interferon alpha-peg-IFN α and ribavirin) on achieving sustained virological response (SVR).MATERIAL AND METHODS:In the study which is comparative, open-label, prospective-retrospective, 70 patients diagnosed with chronic hepatitis C virus infection who met criteria for treatment with standard antiviral therapy combined with anti-lipemic therapy (Atorvastatin 20 mg) were included. Patients in the study were divided into two groups: one group of 35 patients receiving combination therapy (Atorvastatin + peg-IFN α + Ribavirin) and another group of 35 patients received only standard antiviral therapy. Those parameters were followed in all patients: genotyping, quantification of the virus, histological assessment of liver inflammation and fibrosis degree (before starting treatment), the presence of steatosis, laboratory analysis: hematology, liver, lipid and carbohydrate status, insulin blood level (the calculation of HOMA-IR) and body mass index (BMI) calculation. The overall treatment of the patients depends from the virus genotype, thus, patients with genotype 1 and 4 received 48 weeks standard antiviral therapy, but patients with genotypes 2 and 3 received 24 weeks of antiviral therapy. SVR was considered an undetectable level of HCV RNA levels 24 weeks after completion of antiviral therapy. The results were statistically analysed, and all results for p < 0.05 were considered statistically significant.RESULTS:Combination therapy leads to a slightly higher percentage of SVR (85.71%) in patients with chronic hepatitis C versus standard therapy (74.29%), but in a group of patients with genotype 3 this rate of SVR amounting to 95.83%. Combination therapy leads to significant improvement of lipid and glucose status after treatment, and in terms of side effects, there was no appearance of serious adverse events that would be a reason for discontinuation of the therapy.CONCLUSION:Combination therapy Atorvastatin + pegylated interferon alpha + Ribavirin leads to high rate of SVR of 95.83% in patients with chronic hepatitis C, genotype 3. Statins can be used safely in patients with chronic hepatitis C.

Comparative study of efficacy and safety of omega 3 fatty acids and fenofibrate with background atorvastatin therapy in patients of atherogenic dyslipidaemia

Background: Trials of atorvastatin combined either with fenofibrate or with omega-3 fatty acids (O3FA) have shown promising results in atherogenic dyslipidemia but there are very few studies where both these TGs lowering agents have been compared with each other. This study was conducted to compare efficacy and safety of these two agents on lipid profile of patients of atherogenic dyslipidaemia on background statin therapy and also to monitor effects of these interventions on serum uric acid (SUA) levels.Methods: About 90 patients of dyslipidemia were randomised to 3 groups and received O3FA (2000 mg), fenofibrate (80 mg) or dietary restrictions, each with atorvastatin (20 mg) in background for a period of 90 days. Total cholesterol (TC), HDL-C,TGs, LDL-C, SGOT and SGPT levels were done at baseline, 6 weeks and 12 weeks. Other parameters (SUA and BMI) were done at baseline and 12 weeks.Results: Both group 1 (O3FA) and group 2 (fenofibrate) showed highly significant fall in TG levels (p &lt;0.001) in comparison to group 3 (dietary restrictions) whereas comparative TG reduction between groups 1 and group 2 was not significant. Group 2 also showed significant fall in LDL-C levels (p &lt;0.01) in comparison to group 3. LDL-C reduction, TG reduction and SUA reduction was more in group 2 compared to group 1 followed by group 3. No significant difference was observed in the incidence of adverse effects in three study groups.Conclusions: Combination of fenofibrate and atorvastatin was more effective than that of omega-3 fatty acid and atorvastatin, in lowering serum TG and LDL-C levels. There was a significant reduction in SUA levels in all three groups, but combination of fenofibrate and atorvastatin again showed better outcomes. With respect to the safety, all the 3 groups were comparable. O3FA, however, may be a good alternative to fibrates in patients not tolerating latter.

&lt;p&gt;Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets&lt;/p&gt;

Purpose: The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR).Subjects and methods: Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic drug-drug interaction study, was divided into 2 parts. Atorvastatin (40 mg) or metformin (1,000 mg) XR tablets were administered once daily via mono- or co-therapy for 7 days. Plasma levels of atorvastatin and 2-OH-atorvastatin, were quantitatively determined for 36 h in part A (n=50) while metformin plasma concentration was measured up to 24 h in part B (n=16) after the last dosing. Study 2, a randomized, open-labeled, single-dose, two-treatment, two-period, two-sequence crossover study, involved 27 healthy subjects to investigate the impact of food intake on the pharmacokinetics of a combined atorvastatin/metformin XR 20/500 mg (CJ-30056 20/500 mg) tablet.Results: After multiple doses of mono- or co-therapy of atorvastatin (40 mg) and metformin (1,000 mg) XR, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration–time curve during the dosing interval at steady state (AUCτ,ss) were 1.07 (0.94–1.22) and 1.05 (0.99–1.10) for atorvastatin, 1.06 (0.96–1.16) and 1.16 (1.10–1.21) for 2-OH-atorvastatin, and 1.00 (0.86–1.18) and 0.99 (0.87–1.13) for metformin, respectively. Food delayed time to reach maximum concentration (tmax), decreased atorvastatin Cmax by 32% with a GMR (90% CI) of 0.68 (0.59–0.78), and increased metformin AUCt by 56% with a GMR (90% CI) of 1.56 (1.43–1.69).Conclusion: No clinically relevant pharmacokinetic interaction was seen when atorvastatin was co-administered with metformin. Food appeared to change the absorption of atorvastatin and metformin from an FDC formulation. These alterations were in accordance with those described with the single reference drugs when ingested with food.

Two validated stability-indicating chromatographic methods for the separation of two anti-hypertensive combinations in the presence of their degradation products or impurities

Two RP-HPLC methods were developed, optimized, and validated for the determination of two different anti-hypertensive combinations in the presence of their degradation products or impurities and in their pharmaceutical formulations. The first mixture is Ramipril (RAM) in combination with Amlodipine besylate (AML) [mixture I], while the second one is a combination of Ramipril (RAM), Atorvastatin (ATV), and Aspirin (ASP) [mixture II].The proposed combinations were successfully separated on X-bridge C18column (250 × 4.6 mm i.d, 5 µm p.s.), using a mobile phase of 0.05 M phosphate buffer-acetonitrile-THF (60:40:0.1% by volume) pH 2.5 and an isocratic mobile phase formed of acetonitrile-0.05 M phosphate buffer-THF (60:40:0.1% by volume) pH 2.5 for mixture (I) and (II) at a flow rate of 1 mL/min and 1.2 mL/min, respectively. The compromising components of the mixtures were detected at 218 nm. For the best separation of the mentioned components different parameters were examined and optimized. The two suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the quantification of the cited components in presence of their obtained degradation products as well as in their commercial pharmaceutical formulations. For both methods the obtained results were statistically analyzed and compared to those of the official and reported methods; using Student’s t test and F test showing no significant difference with high accuracy and good precision.