No abstract available.
Benzimidazoles ; Blood Pressure ; Stroke ; 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

BACKGROUND: Valsartan is an angiotensin II receptor blocker and is used for patient with hypertension. Although response to valsartan varies each individual, there is no study about factors affecting the variability of valsartan response. METHODS: To investigate the effects of valsartan on the baseline characteristics of blood pressure, single group, open label, pre- and post-comparison clinical study was conducted. Total 21 male Korean volunteers were enrolled. Each subject was administered no drugs in first period and valsartan 80 mg (Diovan HCT) in second period. For pharmacodynamic analysis, 24 hours blood pressure changes were monitored by ambulatory blood pressure monitoring. Twenty-four hour blood pressure changes were matched to valsartan concentration and analyzed by correlation analysis. Changes in blood pressure pattern were also analyzed. Subjects were divided into responder, non-responder, and reverse responder according to pre- and post- 24 hours blood monitoring results. For determination of pharmacokinetic parameters, plasma concentration of valsartan was measured by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters including area under the plasma concentration versus time curve from 0 hour to the last measurable concentration (AUCt), area under the plasma concentration versus time curve extrapolated to infinity, maximum plasma concentration (Cmax), and time required to reach maximum plasma concentration (Tmax) were calculated by noncompartmental models in the BA-CALC 2008 program ver. 1.0.0. RESULTS: There were no significant associations between blood pressure changes and pharmacokinetic parameters of valsartan. Blood pressure pattern change analysis showed significant results. For AUCt, total amount of absorbed valsartan was 25,808 +/- 6,863.0 ng.hr/mL, 20,683 +/- 8,782.7 ng.hr/mL, and 12,502 +/- 5,566.6 ng.hr/mL in responder, non-responder, and reverse responder, respectively (p = 0.041). In C max, maximum concentration of valsartan was 4,314 +/- 1,522.6 ng/mL, 2,588 +/- 1,273.9 ng/mL, and 2,056 +/- 1,075.5 ng/mL, respectively. CONCLUSIONS: These results showed that response to valsartan was not associated with blood concentration in healthy volunteers and changes in blood pressure patterns to valsartan might be associated with the amount of drugs which are absorbed to subjects.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Humans ; Hypertension ; Male ; Mass Spectrometry ; Plasma ; Receptors, Angiotensin ; Tetrazoles ; Valine ; Valsartan

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.
Adult ; Angiotensin Receptor Antagonists ; Biological Availability ; Biphenyl Compounds ; blood ; pharmacokinetics ; Capsules ; Cross-Over Studies ; Humans ; Male ; Tablets ; Tetrazoles ; blood ; pharmacokinetics

BACKGROUND AND OBJECTIVES: Triple anti-platelet therapy may produce more potent inhibition of platelet aggregation in patients undergoing coronary stent implantation. We tested whether this effect could be maintained in diabetic patients, where platelet reactivity is increased and the risk of stent thrombosis is higher. SUBJECTS AND METHODS: Fifty five type 2 diabetic patients who had undergone drug-eluting stent (DES) implantation and chronic anti-platelet therapy (>1 month) were stratified according to the status of anti-platelet therapy. Platelet aggregation after adenosine diphosphate (ADP; 10 micronmol/L and 20 micronmol/L) stimulation was compared using light transmittance aggregometry between dual (aspirin plus clopidogrel, n=34) and triple therapy (aspirin, clopidogrel plus cilostazol, n=21) groups. RESULTS: The 2 groups had similar clinical and procedural characteristics. Maximal ADP-induced platelet aggregation was significantly lower in the triple therapy group than the dual therapy group (ADP 10 micronmol/L, 37.1+/-15.4 vs. 28.3+/-11.8, p=0.03; ADP 20 micronmol/L, 63.1+/-15.0 vs. 49.1+/-15.1, p=0.01), but there were no differences in diabetic treatment (oral hypoglycemic agent vs. insulin) or diabetic control {hemoglobin Alc (HbA1c)< or =7 vs. HbA1c >7}. CONCLUSION: Triple anti-platelet therapy showed more potent inhibition of maximal ADP induced platelet aggregation in type 2 diabetic patients receiving chronic anti-platelet therapy. This finding suggests that triple antiplatelet therapy may be more effective in preventing thrombotic complications after DES implantation in type 2 diabetic patients.
Adenosine Diphosphate ; Blood Platelets ; Diabetes Mellitus ; Drug-Eluting Stents ; Humans ; Light ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; Stents ; Tetrazoles ; Thrombosis ; Ticlopidine

BACKGROUND AND PURPOSE: Cilostazol, a phosphodiesterase III inhibitor, is known to be a useful antiplatelet agent that inhibits the progression of atherosclerosis in ischemic stroke. This study investigated the effects of combining cilostazol with aspirin on the expressions of P-selectin and PAC-1 on activated platelets in acute ischemic stroke. METHODS: We analyzed 70 patients with acute ischemic stroke (<72 hrs of an ischemic event). The daily intake was 100 mg of aspirin in 37 patients and 100 mg of aspirin plus 200 mg of cilostazol in 33 patients. The expressions of P-selectin and PAC-1 on activated platelets were measured on the day of admission and 5 days later. We also evaluated the clinical progression using the National Institutes of Health Stroke Scale (NIHSS) at the same times. RESULTS: After 5 days the extent of PAC-1 expression on activated platelets was significantly lower for combined aspirin and cilostazol treatment (61.0+/-19.3%, p=0.008; mean+/-standard deviation) than the baseline level (70.9+/-12.9%), but did not differ between aspirin alone (66.0 +/-19.0%) and baseline (70.1+/-15.7%). The expression of P-selectin did not differ between combined aspirin and cilostazol treatment and baseline. The clinical progression did not differ between the two groups, as indicated by the absence of significant changes on the NIHSS in the acute period. CONCLUSIONS:This study found that the combined regimen of aspirin and cilostazol exerts the beneficial effect of reducing PAC-1 activity on activated platelets in acute ischemic stroke. However, the clinical outcome of this regimen was no better than that of the aspirin-only regimen. Therefore, further detailed studies of the possible clinical benefits of cilostazol in acute ischemic stroke are needed.
Aspirin ; Atherosclerosis ; Blood Platelets ; Cyclic Nucleotide Phosphodiesterases, Type 3 ; Humans ; National Institutes of Health (U.S.) ; P-Selectin ; Stroke ; Tetrazoles

BACKGROUND/AIMS: A recent clinical trial demonstrated that triple anti platelet therapy resulted in significantly larger minimal luminal diameter and lower restenosis rate compared with conventional therapy after bare metal stent (BMS) implantation. However, it is uncertain that this result will be repeated after drug eluting stent (DES) implantation, especially with low dose cilostazol therapy. Thus, we performed a prospective, randomized study to evaluate the effectiveness of long term triple therapy with low dose cilostazol after DES implantation. METHODS: We analyzed 109 patients (132 lesion) prospectively, who underwent successful coronary DES implantation. The patients were divided into two groups according to combined anti platelet regimen: triple combination of aspirin, clopidogrel, and low dose cilostazol (50 mg/bid) (Group I, n=56) or dual combination of aspirin and clopidogrel (Group II, n=53) for 6 months. The minimal luminal diameter and binary restenosis rate were compared at 6 month follow up by coronary angiogram. The rates of stent thrombosis, major adverse cardiac events (MACE), and bleeding complication were also analyzed. RESULTS: The baseline clinical and angiographic characteristics were not different between the two groups. Angiographic follow-up was performed in 80 patients (109 lesions, 74%). The minimal luminal diameter at 6 month was 2.25+/-0.63 mm in group I and 2.30+/-0.56 mm in group II (p=0.742). Restenosis occurred in 4 patients (7.2%) in group I and 3 patients (5.6%) in group II (p=0.611). There were no differences in the rates of stent thrombosis, MACE, or bleeding complications between the two groups. CONCLUSIONS: Long term triple anti platelet therapy with low dose cilostazol after DES implantation was not effective in obtaining larger minimal luminal diameter or reducing restenosis rate, but it was used safely without increasing bleeding complication.
Aspirin ; Blood Platelets ; Drug-Eluting Stents ; Follow-Up Studies ; Hemorrhage ; Humans ; Phenobarbital ; Prospective Studies ; Stents ; Tetrazoles ; Thrombosis ; Ticlopidine

BACKGROUND: Activation of renin-angiotensin system (RAS) has been an important mechanism of microvascular and macrovascular complications in diabetic patients. It has been reported that RAS blockades reduce the development and progression of diabetic nephropathy. The aim of this study was to evaluate whether valsartan, an angiotensin II receptor blocker (ARB), reduced blood pressure and urinary albumin excretion rate (UAER) in hypertensive type 2 diabetic patients. METHOD: Three hundred forty-seven hypertensive type 2 diabetic patients who had not taken angiotensin converting enzyme inhibitors or ARB for 6 months prior to this study were enrolled. We measured blood pressure and UAER before and after 24 weeks of valsartan treatment. RESULT: Baseline mean systolic and diastolic blood pressure was 143 +/- 15 and 87 +/- 11 mmHg, respectively and the median albumin excretion rate was 27 ug/mg. Reduction in systolic and diastolic blood pressure was 16 mmHg/10 mmHg and the median UAER was 19.3 ug/mg after 24 weeks (P < 0.01, respectively). When we divided the subjects into three groups according to the UAER (normoalbuminuria, microalbuminuria and macroalbuminuria), significant changes were reported in the microalbuminuria and the macroalbuminuria groups. Thirty-eight (42%) patients with microalbuminuria improved to normoalbuminuria and twelve (41%) patients with macroalbuminuria improved to microalbuminuria. We found an association between the improvement of blood pressure and UAER (R = 0.165, P = 0.015). CONCLUSION: We concluded that valsartan reduces urinary albumin excretion and blood pressure in hypertensive type 2 diabetic patients.
Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Blood Pressure ; Diabetes Mellitus ; Diabetic Nephropathies ; Humans ; Receptors, Angiotensin ; Renin-Angiotensin System ; Tetrazoles ; Valine ; Valsartan

BACKGROUND AND OBJECTIVES: Triple anti-platelet therapy is known to prevent restenosis after drug-eluting stent (DES) implantation. However, there is little available data concerning the efficacy of triple anti-platelet therapy for acute myocardial infarction (AMI). SUBJECTS AND METHODS: We analyzed 528 consecutive patients with AMI undergoing DES implantation between Nov 2005 and Apr 2008. We compared clinical outcomes in the triple anti-platelet therapy (group I, n=413: cilostazol combined with aspirin and clopidogrel for at least one month) and dual antiplatelet therapy groups (group II, n=115: aspirin and clopidogrel). RESULTS: There were no significant differences in baseline characteristics. However, ST elevation myocardial infarction (STEMI) and use of TAXUS(R) stents were more common (70.9% vs. 55.7%, p=0.002; 83.5% vs. 73.0%, p=0.011) in Group I. Group I had lower incidences of cardiac death, 6-month target lesion revascularization (TLR), and major adverse cardiac and cerebrovascular events (MACCE) compared to Group II (1.7% vs. 5.7%, p=0.022; 5.7% vs. 11.5%, 0.035; 7.9% vs. 16.0%, p=0.011). On subgroup analysis, the incidence of 6-month TLR was lower among patients with American College of Cardiology/American Heart Association (ACC/AHA) B2 or C lesions and non-STEMI (6.0% vs. 14.9%, p=0.012; 4.3% vs. 19.1%, p=0.002) in Group I compared to those in Group II. The rates of bleeding complications were no different between the two groups. On multivariate analysis, Killip III or IV and triple anti-platelet therapy were independent predictors of 6-month MACCE {hazard ratio (HR)=3.382; 95% confidence interval (CI)=1.384-8.262, HR=0.436; 95% CI=0.203-0.933}. CONCLUSION:Triple anti-platelet therapy is safe and efficacious, and it prevents TLR in patients with AMI, especially those with complex lesions and non-STEMIs.
Aspirin ; Blood Platelets ; Death ; Drug-Eluting Stents ; Heart ; Hemorrhage ; Humans ; Incidence ; Multivariate Analysis ; Myocardial Infarction ; Stents ; Tetrazoles ; Ticlopidine