No abstract available.
Humans ; Simvastatin* ; Ezetimibe

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

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

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 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

BACKGROUND: Simvastatin belongs to the statin family, whose members have immunomodulatory activities. Ezetimibe have synergetic effects when co-administered with simvastatin. In several case reports, alopecia totalis and alopecia universalis were successfully treated with simvastatin/ezetimibe, suggesting that this combination could be a new efficient therapy for recalcitrant alopecia areata (AA). OBJECTIVE: To verify the efficacy of the simvastatin/ezetimibe combination therapy for recalcitrant AA and investigate the relationship between various treatment responses and prognostic factors. METHODS: This prospective open study was performed in patients with recalcitrant AA with the bald surface exceeding 75%. All patients took simvastatin (40 mg) and ezetimibe (10 mg) daily. The extent of hair regrowth expressed as percentage of the bald area was used to evaluate the effectiveness of the therapy. RESULTS: Of 14 enrolled patients, 4 patients (28.6%) were judged as responders showing regrowth of 30% to 80% after 3 months of treatment. The mean age of onset in non-responders was significantly lower than in responders. The total score of prognostic factors, calculated as a sum of factors related to poor prognosis, was much lower in responders than in non-responders. CONCLUSION: The remission rate in this study was unsatisfactory. However, since the recruited patients had not responded to any other treatments for AA, simvastatin/ezetimibe can still be considered as an alternative treatment for recalcitrant AA. The total scores of the prognostic factors were statistically different between responders and non-responders. These results can be used to predict the outcome of treatment with simvastatin/ezetimibe and anticipate prognosis.
Age of Onset ; Alopecia Areata* ; Alopecia* ; Ezetimibe ; Hair ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Prognosis ; Prospective Studies* ; Simvastatin

PURPOSE: To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. MATERIALS AND METHODS: 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson-Trichrome stain. RESULTS: 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. CONCLUSION: As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.
Collagen ; Erythrocytes ; Fibroblasts ; Flow Cytometry ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Parietal Bone ; Rabbits ; Simvastatin ; Transplants ; Water ; Wound Healing

BACKGROUND: Both aspirin and simvastatin are prescribed as treatments or prevention of cardiovascular diseases. The aim of this study was to investigate the influence of simvastatin on pharmacokinetics and pharmacodynamics of aspirin after oral co-administration in healthy subjects. METHODS: Subjects were orally administered aspirin 100 mg for 7 days followed by co-administration of aspirin 100 mg and simvastatin 40 mg for 7 days once daily. A series of blood samples were collected before and till 24hours after drug administration on Day 1 (single-dose of aspirin), Day 7 (multiple-dose of aspirin) and Day 14 (multiple-dose of aspirin and simvastatin). The effects of simvastatin on pharmacokinetics of acetylsalicylic acid and salicylic acid were assessed with the 90 % confidence intervals (CIs) of thegeometric mean ratios (GMRs) of Day 14 over Day 7 for maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-24). Pharmacodynamics was assessed with maximal changes of platelet aggregation from baseline. RESULTS: Twenty-fourhealthy men aged 20 to 36 years were enrolled and 23 of them completed the study. GMRs (90 % CIs) of Cmax and AUC0-24 for acetylsalicylic acid were 1.21 (1.04 - 1.42) and 1.28 (1.19 - 1.38), respectively. For salicylic acid, GMRs of Cmax and AUC0-24 were 0.96 (0.91 - 1.00) and 1.00 (0.97 - 1.04), respectively. Maximal changes of platelet aggregation on Day 7 and Day 14 from baseline were not significantly different (p=0.41); 87.5 +/- 8.8 % and 87.3 +/- 9.2 %, respectively. CONCLUSION: Coadministration of simvastatin slightly increased the systemic exposure of acetylsalicylic acid with no changes of systemic exposure of salicylic acid or inhibition of platelet aggregation.
Aged ; Aspirin ; Cardiovascular Diseases ; Drug Interactions ; Humans ; Male ; Plasma ; Platelet Aggregation ; Salicylic Acid ; 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