No abstract available.
Benzimidazoles ; Blood Pressure ; Stroke ; Tetrazoles

No abstract available.
Percutaneous Coronary Intervention ; Tetrazoles ; Valine ; Ventricular Function, Left ; Valsartan

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 microg/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.
Biotransformation ; Escherichia coli ; Hypertension ; Imidazoles ; Receptors, Angiotensin ; Salmonella typhimurium ; Tetrazoles

Until now restenosis is one of the most important issues after stent implantation. Use of systemic drug therapy to inhibit post-stent restenosis has been largely unsuccessful. Drug-eluting stents (DES) have been shown to significantly reduce restenosis after percutaneous coronary intervention. However we still experience lots of problems associated with restenosis even after DES implantation. Recently some clinical trials have suggested that cilostazol reduces intimal hyperplasia and lowers restenosis after bare metal stents (BMS) implantation. It is uncertain that cilostazol can also reduce restenosis after DES implantation. We need more large clinical trials to elucidate the efficacy of cilostazol on restenosis after DES implantation.
Drug-Eluting Stents ; Hyperplasia ; Percutaneous Coronary Intervention ; Stents ; Tetrazoles

The pharmacokinetics and relative bioavailability were studied in 18 healthy volunteers. A single oral dose of 150 mg irbesartan capsule (test) or tablet (reference) was given to each volunteer according to a randomized 2-way crossover study. The concentrations in plasma were determined by HPLC-UV method. The main parameters of irbesartan capsules were: Cmax: 1.502 +/- 0.295 micrograms/ml, tmax: 1.44 +/- 0.34 h, t 1/2: 20.21 +/- 14.71 h, AUC0-t: 11.087 +/- 3.443 micrograms/ml-1.h. The relative bioavailability of capsule to tablet was (101.4 +/- 28.9)%. The results of statistical analysis showed that two formulations were bioequivalent.
Biological Availability ; Biphenyl Compounds/blood ; Biphenyl Compounds/*pharmacokinetics ; Capsules ; Cross-Over Studies ; Receptors, Angiotensin/*antagonists & inhibitors ; Tablets ; Tetrazoles/blood ; Tetrazoles/*pharmacokinetics

BACKGROUND AND OBJECTIVES: Angiotensin-receptor blockers (ARBs) have beneficial effects on cardiovascular, metabolic, and inflammatory parameters in addition to controlling blood pressure (BP). However, few comparative clinical studies have been conducted with different ARBs. We compared these effects in patients with uncomplicated hypertension who were receiving telmisartan or valsartan. SUBJECTS AND METHODS: The subjects were patients with essential hypertension (48.4+/-9.6 years) who were randomly assigned to take either telmisartan (80 mg/day, n=30) or valsartan (160 mg/day, n=30) for 12 weeks. Their anthropometric, laboratory, vascular, and echocardiographic data were measured at baseline and at the end of the study. RESULTS: Baseline characteristics were not significantly different between the two groups, except for the carotid-femoral pulse wave velocity (cfPWV; telmisartan group vs. valsartan group; 841.2+/-131.0 vs. 761.1+/-104.4 cm/s, p<0.05). After 12 weeks, BP had fallen to a similar extent with mean reductions in the systolic and diastolic BP of 20.7+/-18.1 and 16.3+/-13.0 mm Hg (p<0.001, respectively) for the telmisartan and 22.5+/-17.0 and 16.8+/-9.3 mm Hg (p<0.001, respectively) for the valsartan group. Although the cfPWV and left ventricular mass index (LVMI) fell significantly only with the administration of telmisartan, they were not significantly different when baseline cfPWV was considered. The differences in the cfPWV and LVMI changes from baseline between the two groups were also not significant after adjusting for baseline cfPWV. No significant changes in other vascular, metabolic, or inflammatory parameters were observed with either treatment. CONCLUSION: The effects of a 12-week treatment with the two ARBs, telmisartan and valsartan, on cardiovascular, metabolic, and inflammatory parameters were not different in patients with uncomplicated hypertension.
Benzimidazoles ; Benzoates ; Blood Pressure ; Humans ; Hypertension ; Pulse Wave Analysis ; Tetrazoles ; Valine ; Valsartan

Writing Committee of Korean clinical practice guidelines for secondary prevention of stroke has reviewed recent randomized controlled trials of cilostazol published after the first edition of Korean clinical practice guidelines that considered evidences published before June 2007. Two clinical trials and 1 meta-analysis which compared cilostazol directly with aspirin in the prevention of stroke in patients with cerebral infarction or transient ischemic attack (TIA) were identified and included for the current guideline update. Review of findings indicates that cilostazol as compared to aspirin achieved a greater reduction of stroke as well as composite vascular events of stroke, myocardial infarction, and vascular death. For safety, cilostazol was associated with fewer major bleeding events than aspirin. Accordingly, new recommendations for cilostazol are made for prevention of stroke in the setting of noncardioembolic stroke or TIA. Changes in the guidelines necessitated by new evidences will be continuously reflected in future guidelines.
Aspirin ; Cerebral Infarction ; Hemorrhage ; Humans ; Ischemic Attack, Transient ; Myocardial Infarction ; Secondary Prevention ; Stroke ; Tetrazoles ; Writing

BACKGROUND: Olmesartan medoxomil is an angiotensin II receptor blocker commonly used in hypertension. First objective of this study was to evaluate the bioequivalence of two olmesartan formulations, Olmesartan 20 mg and 40 mg tablet (Yuhan, Pharmaceutical Corp. Seoul, Korea) as test drugs and Olmetec(R) 20 mg and 40 mg tablet (Daewoong, Pharmaceutical Corp. Seoul, Korea) as reference drugs. Second objective of this study was to evaluate the dose-proportionality of two formulations. METHODS: Two studies (20 mg, 40 mg) were conducted as a randomized, open-label, 2-period, crossover design. Each subject received one 20 mg or 40 mg tablet of the reference or test formulation of olmesartan medoxomil in each study. Blood samples were obtained during the 48-hour period after the dose in each treatment period. Wash-out period was 1 week in each study. Concentrations of olmesartan medoxomil in plasma were analyzed using a liquid chromatography system with tandem mass-spectrometric detection (LC/MS/MS). The primary pharmacokinetic parameters were Cmax (maximum concentration) and AUCt (area under the concentration-time curve from time 0 to the last sampling time). RESULTS: A total number of 40 healthy male volunteers participated in the study and 37 volunteers completed both treatment periods in 20 mg trial. All 40 participants completed both treatment periods in 40 mg trial. The 90 % CIs for the geometric mean ratios of the pharmacokinetic parameters (test:reference drug) were 0.93 ~ 1.04 for AUCt and 0.97 ~ 1.08 for Cmax in 20 mg trial. The 90 CIs were 0.94 ~ 1.02 for AUCt and 1.00 ~ 1.11 for Cmax in 40 mg trial. All parameters of two studies satisfy the range of bioequivalence criterion. CONCLUSION: The obtained results indicated that pharmacokinetic exposure to Olmesartan 20 mg and 40 mg tablet was bioequivalent to that of Olmetec(R) 20 mg and 40 mg tablet, respectively.
Chromatography, Liquid ; Cross-Over Studies ; Humans ; Hypertension ; Imidazoles ; Male ; Plasma ; Receptors, Angiotensin ; Tetrazoles ; Therapeutic Equivalency

Although anti-atherogenic effects of cilostazol have been suggested, its effects on the expression of SR in macrophages are unclear. This study investigated the role of cilostazol on CD36 expression of murine macrophages enhanced by HNE, a byproduct of lipid peroxidation. The stimulation of macrophages with HNE led to an increased expression of CD36, which was significantly attenuated by NAC, an antioxidant. Moreover, the increased production of ROS by HNE was completely abolished by NADPH oxidase inhibitors, DPI and apocynin, as well as by the 5-LO inhibitor, MK886, but not by inhibitors for other oxidases. This suggested that NADPH-oxidase and 5-LO were major sources of ROS induced by HNE. In addition, HNE-enhanced expression of CD36 was reduced by these inhibitors, which indicated a role for NADPH oxidase and 5-LO on CD36 expression. In our present study, cilostazol was a significant inhibitor of ROS production, as well as CD36 expression induced by HNE. An increase in NADPH oxidase activity by HNE was significantly attenuated by cilostazol, however cilostazol had no effect on HNE-enhanced 5-LO activity. Together, these results suggest that cilostazol attenuates HNE-enhanced CD36 expression on murine macrophages thorough inhibition of NADPH oxidase-derived ROS generation.
Acetophenones ; Lipid Peroxidation ; Macrophages ; NADP ; NADPH Oxidase ; Oxidoreductases ; Reactive Oxygen Species ; Tetrazoles

Olmesartan,an angiotensin Ⅱ receptor blocker,is a commonly used antihypertensive drug.Several case reports and cohort studies in recent years have described a severe gastrointestinal adverse event with chronic diarrhea,intestinal malabsorption,and weight loss after the administration of olmesartan.In such cases,the patients recovered after discontinuing olmesartan.This adverse effect is called olmesartan-associated enteropathy(OAE).This article reviews the potential pathogenesis and clinical characteristics of OAE,which broadens the disease spectrum for the differential diagnosis of chronic diarrhea and intestinal malabsorption.
Angiotensin Receptor Antagonists ; Humans ; Imidazoles ; Intestinal Diseases/diagnosis* ; Tetrazoles/adverse effects*