AIMTo study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule.

METHODSFollowing oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed.

RESULTSThe concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240.

CONCLUSIONThe high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.

Administration, Oral ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacokinetics ; Biological Availability ; Capsules ; Dogs ; Female ; Probucol ; administration & dosage ; pharmacokinetics ; Random Allocation ; Tablets

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

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

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

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

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

OBJECTIVEPatients with coronary artery disease (CAD, stenosis between 50% - 70% evidenced by coronary angiography) were treated with atorvastatin 40 mg (n = 19) or atorvastatin 10 mg in combination with ezetimibe 10 mg (n = 23). Blood lipid profile and metalloproteinases were monitored up to 3 months.

METHODSCholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), liver function, renal function, creatine kinase, MMP-2, MMP-9, TIMP-1 were measured at baseline and at 1 month and 3 months post therapy.

RESULTS(1) At 3 months, LDL-C was similarly reduced in monotherapy group [(1.94 +/- 0.49) mmol/L, 37.82% reduction compared to baseline] and in combined therapy group [(1.92 +/- 0.54) mmol/L, 38.26% reduction compared to baseline]. (2) AST, ALT, renal function and creatine kinase remained unchanged post various therapy (all P > 0.05). (3) MMP-2, MMP-9 significantly decreased and TIMP-1 significantly increased at 3 months compared to baseline in monotherapy group but these parameters remained unchanged in combined therapy group.

CONCLUSIONBoth therapy regimens were well tolerated and similarly effectively reduced blood lipids and 40 mg atorvastatin monotherapy regimen is superior to atorvastatin 10 mg plus ezetimibe 10 mg regimen in improving metalloproteinases parameters.

Adolescent ; Adult ; Aged ; Anticholesteremic Agents ; administration & dosage ; therapeutic use ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; therapeutic use ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Artery Disease ; drug therapy ; metabolism ; Drug Therapy, Combination ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Hypolipidemic Agents ; administration & dosage ; therapeutic use ; Male ; Metalloproteases ; blood ; Middle Aged ; Pyrroles ; administration & dosage ; therapeutic use ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Treatment Outcome ; Young Adult

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