The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.
Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Atorvastatin Calcium ; administration & dosage ; blood ; pharmacokinetics ; Biological Availability ; Cross-Over Studies ; Dogs ; Drug Interactions ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; blood ; pharmacokinetics ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Random Allocation ; Thiazolidinediones ; administration & dosage ; blood ; pharmacokinetics

INTRODUCTIONWe aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.

METHODSA double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.

RESULTSOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.

CONCLUSIONCombination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.

Anti-Inflammatory Agents ; therapeutic use ; Anticholesteremic Agents ; administration & dosage ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Dyslipidemias ; drug therapy ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; Humans ; Hypolipidemic Agents ; therapeutic use ; India ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; Treatment Outcome

ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I (apoA-I), and plays a key role in the initial steps of the whole process of reverse cholesterol transport (RCT). Upregulation of ABCA1 is beneficial for atherosclerosis (AS) prevention and/or therapy, which indicated that ABCA1 was a target for anti-AS drug development. In the previous study, a high-throughput screening method was established using ABCA1p-LUC HepG2 cell line to find the upregulators of ABCA1. In the present study, compound 2030421B was found using this method, with EC50 of 0.50 microg x mL(-1). The compound was further identified as an upregulator of ABCA1 expression by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis. Studies also showed that the 2030421B could induce apoA-I-mediated cholesterol efflux and inhibit lipids uptake into mouse peritoneal macrophages RAW264.7.
ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Animals ; Anticholesteremic Agents ; administration & dosage ; chemistry ; pharmacology ; Apolipoprotein A-I ; metabolism ; Benzaldehydes ; administration & dosage ; chemistry ; pharmacology ; Biological Transport ; Cells, Cultured ; Cholesterol ; secretion ; Dose-Response Relationship, Drug ; Hep G2 Cells ; High-Throughput Screening Assays ; Humans ; Lipid Metabolism ; Lipids ; analysis ; Macrophages, Peritoneal ; cytology ; metabolism ; Mice ; Molecular Structure ; RNA, Messenger ; Up-Regulation ; drug effects

This study is to observe anti-lipotoxic effect of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet. Thirty-four complex model rats were induced by two-kidney, one-clip method and on high-fat and refined-carbohydrate diet for thirteen weeks. From the fifth week, intragastric administration of sesamin (120, 60 and 30 mg x kg(-1) x d(-1)) lasted for eight weeks. Blood pressure (BP), blood fat (BF), blood glucose (BG), free fatty acids (FFA), insulin (Ins), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were determined. Pathological changes of pancreas, perirenal fat and liver were semiquantitatively analyzed. In sesamin (120 and 60 mg x kg(-1) x d(-1)) group, it was found that there were decrease of levels of BP, BF, BG, TNF-alpha, IL-6 and FFA, improvement of insulin resistance and glucose tolerance, alleviation of body weight, humid weight of fat, liver and pancreas and their organ index, and reduction of islet cell hyperplasia and amount of lipid droplet vacuoles in lipocyte and hepatocyte. It is implied that sesamin had anti-lipotoxic effect and its mechanism may be closely associated with the amelioration of insulin resistance via reducing lipidoses in hepatocyte and inflammatory adipokines such as TNF-alpha and IL-6.
Adipocytes ; drug effects ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacology ; Antihypertensive Agents ; administration & dosage ; pharmacology ; Blood Glucose ; metabolism ; Blood Pressure ; drug effects ; Body Weight ; drug effects ; Cholesterol ; blood ; Diet, High-Fat ; Dioxoles ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Fatty Acids, Nonesterified ; blood ; Glucose Tolerance Test ; Hypertension, Renovascular ; blood ; pathology ; Insulin ; blood ; Insulin Resistance ; Interleukin-6 ; blood ; Islets of Langerhans ; pathology ; Lignans ; administration & dosage ; pharmacology ; Liver ; pathology ; Male ; Pancreas ; pathology ; Rats ; Rats, Sprague-Dawley ; Sucrose ; Triglycerides ; blood ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo evaluate whether taking atorvastatin for long time has positive effects on age-related renal impairment.

METHODS20-month-age normal female Wistar rats were divided into three groups (n = 9). First group were fed atorvastatin 10 mg/(kg x d). Second group were fed atorvastatin 1 mg/(kg x d). Third group were fed the same volume normal saline served as control. All the rats were sacrificed after four months. 3-month-age normal female Wistar rats (n = 9) also served as normal control. Kidney weight, serum creatinine (Scr) and blood-lipoids were measured. Paraffin sections of renal tissues were stained with PAS and Sirius red. Sclerosis index of glomerulus was calculated.

RESULTSRenal mass diminution was found in all the groups of aging rats. Scr was decreased in the group of aging rats with atorvastatin 1 mg/(kg x d). The level of blood-lipoids of aging rats was higher than that of young rats. The level of serum cholesterol and low-density lipoprotein (LDL) were decreased in first group (both P < 0.05) and only LDL decreased in second group (P < 0.05). Morphological changes of aging kidney were focal segmental glomerulosclerosis, widen of mesangial region, infiltration of inflammatory cells and sclerosis of arteriole. The treatment of atorvastatin improved the pathologic changes in the aging rats significantly, especially in the first group.

CONCLUSIONTaking atorvastatin for long time can notably improve the pathological changes of aging kidney. All these effects may be induced by lowing of blood-lipoids, relieving the sclerosis of renal arteriole and reducing the infiltration of inflammatory cells.

Aging ; physiology ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacology ; Arteriosclerosis ; pathology ; prevention & control ; Atorvastatin Calcium ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; Kidney ; pathology ; Kidney Diseases ; prevention & control ; Pyrroles ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; Renal Artery ; pathology

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm2 vs. 1.69+/-0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.
Animals ; Anticholesteremic Agents/administration & dosage ; Azetidines/*administration & dosage ; Coronary Restenosis/diagnosis/drug therapy/*etiology ; *Disease Models, Animal ; Drug Combinations ; Drug Implants/administration & dosage ; Drug-Eluting Stents/*adverse effects ; Female ; Graft Occlusion, Vascular/diagnosis/*drug therapy/*etiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Simvastatin/*administration & dosage ; Swine ; Treatment Outcome

OBJECTIVETo investigate the impacts of Xuezhikang (XZK) or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells (CEPCs) in essential hypertensive (EH) patients.

METHODSEighty-eight EH patients were enrolled into the study and randomly assigned to the antihypertensive drug treatment group (ATH group, 29 cases), the pravastatin treatment group (PRA group, 29 cases) and the Xuezhikang treatment group (XZK group, 30 cases). Patients in the 3 groups were treated with routine antihypertensive drugs. In addition, pravastatin and Xuezhikang were given to the patients in the PRA group and XZK group, respectively. After an eight-week treatment, CEPCs were counted using a laser scanning confocal microscope, and their proliferation function was evaluated by the MTT colorimetric assay and the adherent cell number was counted to estimate the adhesion function.

RESULTSAfter the treatment, CEPCs in the PRA group (116.60+/-5.70) and XZK group (114.40+/-6.55) was significantly higher than that in the ATH group (88.00+/-6.32, P<0.01). CEPCs proliferation capability and the adhesion function in the PRA group (0.406+/-0.016, 33.60+/-4.26) and XZK group (0.415+/-0.018, 34.30+/-3.77) were obviously superior to those in the ATH group (0.333+/-0.021, P<0.01; 23.30+/-3.19, P<0.01). No significant difference was found between the pravastatin group and the XZK group.

CONCLUSIONSCombined use of XZK or pravastatin with the anti-hypertensive therapy could increase the CEPCs number and improve their function in EH patients with the blood pressure controlled by antihypertensive drugs, leading to benefits independent of pressure-lowering effects.

Aged ; Anticholesteremic Agents ; administration & dosage ; Antidiuretic Agents ; administration & dosage ; Antihypertensive Agents ; administration & dosage ; Blood Cell Count ; Calcium Channel Blockers ; administration & dosage ; Cell Adhesion ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Endothelial Cells ; drug effects ; pathology ; physiology ; Female ; Humans ; Hypertension ; blood ; drug therapy ; pathology ; physiopathology ; Integrative Medicine ; methods ; Male ; Middle Aged ; Pravastatin ; administration & dosage ; Stem Cells ; drug effects ; pathology ; physiology

OBJECTIVETo study lipid-regulating action of 2, 3, 5, 4'-tetrahydroxy stilbene-2-O-beta-D-glucopyranoside (TSG) from Polygonum multiflorum on experimental model hyperlipidemic rats.

METHODTSG 90 and 180 mg x kg(-10 x d(-1), atorvastatin mg kg(-1) x d(-1) and saline 2 mL x d(-1) were administered to hyperlipidemic rats. Groups of rats were determined and compared with those of saline group. The LDLR and HMGR mRNA expression were also detected.

RESULTTSG significantly reduced serum TC and LDL-C level and atherosclerosis index, increased the expression of LDLR in the liver cells.

CONCLUSIONTSG, which shows effects and mechanism in part like atorcastatin, is a major constituent with blood-lipid regulating effect of P. multiflorum and can be explored as a potent medication for hyperlipidemia. Effects on LDL-C and AI, as well as on gene expression of TSG were first reported.

Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacology ; Atorvastatin Calcium ; Cholesterol, LDL ; blood ; Glucosides ; administration & dosage ; isolation & purification ; pharmacology ; Hepatocytes ; cytology ; drug effects ; metabolism ; Heptanoic Acids ; administration & dosage ; pharmacology ; Hydroxymethylglutaryl CoA Reductases ; biosynthesis ; genetics ; Hyperlipidemias ; blood ; prevention & control ; Male ; Plant Tubers ; chemistry ; Plants, Medicinal ; chemistry ; Polygonum ; chemistry ; Pyrroles ; administration & dosage ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, LDL ; biosynthesis ; genetics ; Stilbenes ; administration & dosage ; isolation & purification ; pharmacology ; Triglycerides ; blood

beta-Glucan is a polysaccharide in the form of fiber and the main element of fiber in grains such as barley, oats, yeast and mushrooms. Many studies have examined the efficacy of beta-Glucan in terms of the lipid lowering effects, blood sugar reduction, weight reduction, immune modulator, and anticarcinogenic effect. However, there is no comprehensive review article on the biomedical issues regarding beta-Glucan. The authors searched for systematic reviews and clinical experiments for each relevant topic and reviewed the biomedical effects of beta-Glucan, for the purpose of developing research strategies for the future.
beta-Glucans/administration & dosage/*pharmacology/therapeutic use ; Neoplasms/drug therapy ; Infection/drug therapy ; Humans ; Dose-Response Relationship, Drug ; Dietary Supplements ; Dietary Fiber/administration & dosage/*pharmacology/therapeutic use ; Cholesterol/blood ; Body Weight/drug effects ; Blood Glucose/analysis ; Anticholesteremic Agents/pharmacology ; Animals

OBJECTIVETo investigate the effect of early intervention by pravastatin with two different dosage on inflammatory factors and endothelial vasodilator function in patients with unstable angina (UA).

METHODS108 patients with UA were investigated consecutively and divided randomly into three groups (group 20 mg, n = 37; group 10 mg, n = 37; group control, n = 34). Blood samples were examined at admission and 4, 8 weeks after the therapy of pravastatin. Fourty patients of UA were chosen from those three groups (15, 15 and 10 cases respectively). The endothelium-dependent vasodilation and the function of vascular endothelium of them were measured. In the dosage of 20 mg pravastatin group non-endothelium-dependent vasodilation in brachial artery was also tested by ultrasound before and 8 weeks after the therapy. Cardiac events were followed up for 2 months.

RESULTS(1) The use of pravastatin in early admission period of UA could significantly reduce inflammatory factors and improve vascular endothelium function, which was more obviously in the group of 20 mg/d than in group of 10 mg/d. These benefits occurred in 4th week and more obviously in 8th week after the therapy. (2) The lipid lowering therapy in the early stage of admission (24 - 48 h) resulted in the reduction of cardiac events in the hospital.

CONCLUSIONThe use of pravastatin 20 mg/d seems better than that of 10 mg/d in all the fields as above in early admission period of UA patients.

Adult ; Aged ; Angina, Unstable ; drug therapy ; Anticholesteremic Agents ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Inpatients ; Male ; Middle Aged ; Pravastatin ; administration & dosage ; therapeutic use ; Prospective Studies