Background: Statin and its derivate (simvastatin, autorvastatin, etc...) are used for dyslipidemia treatment and preventing thrombose. However, the mechanism of the antithrombotic action is still being studied. Objectives: (1) To study coagulation parameters in dyslipidemia. (2) To evaluate the effects of simvastatin on coagulation parameters in dyslipidemia patients. Subject and Method: A prospective study was carried out in a sample of 22 patients with primary hypercholesterolemia (type IIa), who were treated with simvastatin 20mg/d for 1 month. The lipid parameters (cholesterol, triglycerid, HDL, LDL) and coagulation parameters (PT, APTT, fibrinogen, factor II, V, VII, X, VIII, IX, XI) were compared between pre and post therapy, and to the control group (59 healthy people). Results: Most of coagulation parameter values (except factor VIII and X) of the pre treatment group were significantly change towards hypercoagulation (p<0.05%) when compared to the control group. After treatment, PT rate, APTT, APTT rate, fibrinogen, factor VII and IX were significantly changed towards coagulation when compared to pre treatment (p<0.05%). The plasma coagulation and lipid parameters of more than 50% of the hypercholesterolemia patients returned to normal values after treatment. Conclusions: Simvastatin therapy on dyslipidemia patients can reduce not only the level of serum lipid, but also coagulation, and proved its effectiveness in the prevention of thrombosis.
Simvastatin ; coagulation ; dyslipidemia

No abstract available.
Humans ; Simvastatin* ; Ezetimibe

Objectives: Bioequivalence studies provide evidence that generic drugs can produce the same blood levels as the innovator, suggesting similar efficacy and safety and indicating interchangeability without the need to titrate dosing. This study aimed to compare the rate and extent of absorption of two simvastatin 20 mg tablets of Pascual Laboratories, Inc. with two Zocor 20 mg tablets of Merck Sharp & Dohme (I.A.) Corp. in healthy Filipinos. The study also monitored the safety and tolerability of the medications, under the same conditions. Proof of bioequivalence is required by FDA Philippines to establish the interchangeability of generic products and their innovators. Methods: Twenty-four healthy participants were administered with a single oral dose of two 20 mg simvastatin tablets under fasting conditions, in a randomized, open-label, blind-endpoint analysis, two-way crossover study, with a washout period of one week. Pharmacokinetic blood sampling was done up to 24 h post-dose. Simvastatin was measured using Liquid Chromatography-Tandem Mass Spectrometry with a validated method. The geometric mean ratios for maximum plasma concentration (Cmax) and area under the plasma-concentration-time curve from time zero to the last observed concentration at time 24 h (AUC0-24) were used for bioequivalence. Results: All 24 participants, 12 males and 12 females, completed the study. Mean age was 24.21 years, mean weight was 58.81 kg, and mean BMI was 23.16 kg/m2. The ratios of Cmax and AUC0-24 were 102.17% (90% CI: 89.19-117.03), and 101.29% (90% CI: 86.87-118.10), respectively, and were both within the bioequivalence limits of 80% to 125%. No adverse event was reported and both formulations were well-tolerated. Conclusions Simvastatin 20 mg tablet of Pascual Laboratories, Inc. and the innovator Zocor 20 mg tablet are bioequivalent. Single two-tablet doses of both products are safe and well tolerated.
Simvastatin ; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Radiation recall dermatitis gap (RRD) is the development of an inflammatory reaction throughout a previously irradiated area, precipitated by the administration of certain drugs. Usually chemotherapeutic agents have been associated with RRD, but other drugs reported include tamoxifen, interferon alfa-2b, simvastatin, and antituberculous drugs. We present a case of RRD after chemotherapy with letrozol (Femara(R)). Letrozol is a third generation aromatase inhibitor, which acts as an anti-estrogen agent. This is the first reported case of RRD triggered by letrozol.
Aromatase ; Drug Therapy ; Interferons ; Radiodermatitis* ; Simvastatin ; Tamoxifen

BACKGROUND AND OBJECTIVES: The inhibition of cholesterol absorption by ezetimibe increases cholesterol synthesis. The effect of inhibition of cholesterol synthesis on cholesterol absorption is controversial. The influence of these interactions on cholesterol levels is unknown. We investigated on the extent to which cholesterol levels were affected by the reaction of one pathway to the inhibition of the other pathway. SUBJECTS AND METHODS: This case-controlled study enrolled 198 patients who needed cholesterol-lowering drugs. Ezetimibe (10 mg) was administered to the patients with (n=58) and without on-going statin therapy (n=58). Simvastatin (20 mg) was administered to the patients treated with (n=41) and without ezetimibe (n=41). RESULTS: Ezetimibe without statin lowered the total cholesterol by 13.3+/-8.8% (p<0.001) and the low density lipoprotein-cholesterol (LDL-C) by 18.7+/-15.3% (p<0.001). Ezetimibe added to statin decreased the total cholesterol by 21.1+/-7.7% (p<0.001) and the LDL-C by 29.9+/-12.6% (p<0.001). The total cholesterol and LDL-C were reduced more by ezetimibe in patients with statin therapy than in those without statin therapy (p<0.001 and p<0.001, respectively). The differences in the effect of simvastatin on total cholesterol and LDL-C between the patients with and without ezetimibe showed borderline significance (p=0.10 and p=0.055, respectively). CONCLUSION: A prior inhibition of cholesterol synthesis by statin enhanced the effect of ezetimibe on total cholesterol and LDL-C by 7.8% and 11.2%, respectively. This finding suggests that ezetimibe increased cholesterol synthesis, resulting in a significant elevation of cholesterol levels.
Absorption ; Case-Control Studies ; Cholesterol ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Lipoproteins ; Simvastatin ; Ezetimibe

Methimazole and prophylthiouracil are commonly prescribed for patients with hyperthyroidism. The serious side effect of toxic hepatitis caused by these two drugs is well known. According to recent Korean and American management guidelines for hyperthyroidism, mehimazole is recommended as the first-choice antithyroid drug for the treatment of hyperthyroidism. Toxic hepatitis rarely occurs in methimazole users. We report a rare case of a 52-year-old female with toxic hepatitis after methimazole use that had past medical history of simvastatin induced liver injury.
Drug Interactions ; Drug-Induced Liver Injury ; Female ; Hepatitis* ; Humans ; Hyperthyroidism ; Liver* ; Methimazole ; Middle Aged ; Simvastatin

BACKGROUND AND OBJECTIVES: The beneficial effects of statins in preventing cardiovascular events may depend, in part, on their anti-inflammatory action. We previously reported that low dose statin therapy has cholesterol lowering effects, but no effect on inflammation, and proposed that a sufficient dose of therapy might be needed to achieve anti-inflammatory action. The aims of this study were to confirm the suggestions made in our previous study. SUBJECTS AND METHODS: Fifteen unstable angina patients who were enrolled in our previous study were evaluated. The usual dose (20 mg) of simvastatin was administrated for 26 weeks, blood samples collected following the administration and tested for their lipid profiles and inflammatory markers (IL-6, CRP). The changes in the lipid profiles and inflammatory markers, from baseline levels, to the usual and low doses of statin therapy were evaluated. RESULTS: The changes in the IL-6 and hsCRP levels after the usual dose simvastatin therapy compared with the baseline levels were -72.8 and -59.6% (p< 0.05), respectively. The changes in the IL-6 and hsCRP levels after the usual dose simvastatin therapy compared with a 5 mg dose were -77.2 and -47.1% (p< 0.05), respectively. There was statistically significant correlation between the change in the levels of IL-6 and hsCRP during statin therapy. CONCLUSION: Our data confirmed the preliminary result of Chung et al, which suggested the usual dose of simvastatin is required to inhibit the inflammation of unstable plaque in patients with unstable angina associated with hypercholesterolemia.
Angina, Unstable* ; C-Reactive Protein ; Cholesterol ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Inflammation ; Interleukin-6* ; Simvastatin*

OBJECTIVE: To evaluate the effects of simvastatin on the proliferation and apoptosis of human endometrial cells from women with endometriosis. METHODS: Endometrial tissues were obtained from four women with endometriosis. The endometrial stromal cells isolated from tissue were cultured with 0, 2 and 10 micrometer simvastatin treatments for 48 hours. The proliferation of endometrial stromal cells was inhibited with 2 and 10 micrometer simvastatin treatments compared to control. The effect of simvastatin on the sub-G1 phase of cell cycle was determined by flow cytometry. The expression of apoptosis related molecule (Bcl-2, Bax and caspase-3) was examined in control and simvastatin treatments using western blot. RESULTS: The sub-G1 phase was higher in 10 micrometer simvastatin than in control and 2 micrometer simvastatin (P<0.05). This result showed that simvastatin could induce apoptosis of stromal cells. The expression of Bcl-2 was increased in simvastatin treatments slightly (P<0.05) and the expression of Bax was not different between control and experimental groups. The activation of caspase-3 was significantly higher in 10 micrometer simvastatin treated group than control and 2 micrometer simvastatin treated groups (P<0.05). CONCLUSION: Simvastatin induces apoptosis of endometrial stromal cells and inhibits their proliferation. It was considered that simvastatin could potentially be a therapeutic agent for the treatment of endometriosis.
Apoptosis ; Caspase 3 ; Cell Cycle ; Endometriosis ; Female ; Flow Cytometry ; Humans ; Simvastatin ; Stromal Cells

BACKGROUND: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. METHODS: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-alpha, TNF-a and interleukin-1beta, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. RESULTS: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. CONCLUSION: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.
Airway Remodeling ; Collagen ; Contracts ; Cytokines ; Fibroblasts ; Humans ; Interleukin-1beta ; Leukocyte Elastase ; Lung ; Matrix Metalloproteinases ; Necrosis ; Simvastatin

Among the side effects of simvastatin, elevated liver enzyme or creatine kinase activity has been occasionally report-ed, but overt myopathy is rare. We report two cases of simvastatin-induced myopathy with usual dosages of simvas-tatin. Two patients presented with general myalgia, markedly elevated creatine kinase activity, and mild proximal weak-ness. One patient had been treated with concomitant use of cyclosporine and simvastatin after renal transplantation, and another patient had diabetic nephropathy. We recommend careful monitoring when myalgia appears in a patient receiv-ing simvastatin. (J Korean Neurol Assoc 19(4):435~437, 2001)
Creatine Kinase ; Cyclosporine ; Diabetic Nephropathies ; Humans ; Kidney Transplantation ; Liver ; Muscular Diseases* ; Myalgia ; Simvastatin