No abstract available.
Amlodipine

Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (C(max)) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for C(max) and area under the concentration-time curve from time 0 to the last quantifiable time point (AUC(last)) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for C(max) and AUC(last) were 1.0440 (0.9202–1.1844) and 1.0412 (0.9775–1.1090) for fimasartan, and 1.0430 (1.0156–1.0711) and 1.0339 (1.0055–1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for C(max) and AUC(last) of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence.
Amlodipine ; Antihypertensive Agents ; Cross-Over Studies ; Healthy Volunteers ; Hypertension ; Pharmacokinetics ; Plasma ; Therapeutic Equivalency

OBJECTIVES: Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR). METHODS: Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg·d) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg·d), taking WistarKyoto(WKY) as normal control (=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR. RESULTS: After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (<0.05). CONCLUSIONS The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.
Amlodipine ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Benzazepines ; pharmacology ; Blood Pressure ; Hypertension ; drug therapy ; Male ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Secretin ; metabolism ; Somatostatin ; metabolism

No abstract available.
Amlodipine*

No abstract available.
Amlodipine*

BACKGROUND/AIMS: Oxidative stress plays an important role in the pathogenesis and progression of diabetic complications and antagonists of renin-angiotensin system and amlodipine have been reported previously to reduce oxidative stress. In this study, we compared the changes in oxidative stress markers after valsartan and amlodipine treatment in type 2 diabetic patients with hypertension and compared the changes in metabolic parameters. METHODS: Type 2 diabetic subjects with hypertension 30 to 80 years of age who were not taking antihypertensive drugs were randomized into either valsartan (n = 33) or amlodipine (n = 35) groups and treated for 24 weeks. We measured serum nitrotyrosine levels as an oxidative stress marker. Metabolic parameters including serum glucose, insulin, lipid profile, and urine albumin and creatinine were also measured. RESULTS: After 24 weeks of valsartan or amlodipine treatment, systolic and diastolic blood pressure decreased, with no significant difference between the groups. Both groups showed a decrease in serum nitrotyrosine (7.74 ± 7.30 nmol/L vs. 3.95 ± 4.07 nmol/L in the valsartan group and 8.37 ± 8.75 nmol/L vs. 2.68 ± 2.23 nmol/L in the amlodipine group) with no significant difference between the groups. Other parameters including glucose, lipid profile, albumin-to-creatinine ratio, and homeostasis model assessment of insulin resistance showed no significant differences before and after treatment in either group. CONCLUSIONS: Valsartan and amlodipine reduced the oxidative stress marker in type 2 diabetic patients with hypertension.
Amlodipine* ; Antihypertensive Agents ; Blood Glucose ; Blood Pressure ; Creatinine ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Glucose ; Homeostasis ; Humans ; Hypertension* ; Insulin ; Insulin Resistance ; Oxidative Stress* ; Renin-Angiotensin System ; Valsartan*

BACKGROUND/AIMS: Oxidative stress plays an important role in the pathogenesis and progression of diabetic complications and antagonists of renin-angiotensin system and amlodipine have been reported previously to reduce oxidative stress. In this study, we compared the changes in oxidative stress markers after valsartan and amlodipine treatment in type 2 diabetic patients with hypertension and compared the changes in metabolic parameters. METHODS: Type 2 diabetic subjects with hypertension 30 to 80 years of age who were not taking antihypertensive drugs were randomized into either valsartan (n = 33) or amlodipine (n = 35) groups and treated for 24 weeks. We measured serum nitrotyrosine levels as an oxidative stress marker. Metabolic parameters including serum glucose, insulin, lipid profile, and urine albumin and creatinine were also measured. RESULTS: After 24 weeks of valsartan or amlodipine treatment, systolic and diastolic blood pressure decreased, with no significant difference between the groups. Both groups showed a decrease in serum nitrotyrosine (7.74 ± 7.30 nmol/L vs. 3.95 ± 4.07 nmol/L in the valsartan group and 8.37 ± 8.75 nmol/L vs. 2.68 ± 2.23 nmol/L in the amlodipine group) with no significant difference between the groups. Other parameters including glucose, lipid profile, albumin-to-creatinine ratio, and homeostasis model assessment of insulin resistance showed no significant differences before and after treatment in either group. CONCLUSIONS: Valsartan and amlodipine reduced the oxidative stress marker in type 2 diabetic patients with hypertension.
Amlodipine* ; Antihypertensive Agents ; Blood Glucose ; Blood Pressure ; Creatinine ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Glucose ; Homeostasis ; Humans ; Hypertension* ; Insulin ; Insulin Resistance ; Oxidative Stress* ; Renin-Angiotensin System ; Valsartan*

This study describes the development of an analytical method to determine radotinib levels in human plasma using high performance liquid chromatography (HPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) for pharmacokinetic application. Plasma samples were sequentially processed by liquid-liquid extraction using methyl tert-butyl ether, evaporation, and reconstitution. Analytes were separated and analyzed using HPLC-MS/MS in selected reaction monitoring mode, monitoring the specific transitions of m/z 531 to 290 for radotinib and m/z 409 to 238 for amlodipine (internal standard). The HPLC-MS/MS analytical method was validated with respect to selectivity, linearity, sensitivity, accuracy, precision, recovery, and stability. Calibration curves were linear over a concentration range 5–3,000 ng/mL with correlation coefficients (r) > 0.998. The lower limit of quantification for radotinib in plasma was 5 ng/mL. The accuracy and precision of the analytical method were acceptable within 15% at all quality control levels. This method was suitable to determine radotinib levels in human plasma because of its simplicity, selectivity, precision, and accuracy.
Amlodipine ; Calibration ; Chromatography, Liquid ; Ether ; Humans* ; Liquid-Liquid Extraction ; Mass Spectrometry* ; Methods* ; Plasma* ; Quality Control ; Tandem Mass Spectrometry

Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine (10⁻¹⁰–10⁻³ M) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside (10⁻¹⁰–10⁻³ M) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.
Acetylcholine ; Administration, Oral ; Amlodipine ; Animals ; Aorta ; Aralia* ; Blood Pressure ; Ethanol* ; Hypertension ; Lipid Peroxidation ; Malondialdehyde ; Nitroprusside ; Norepinephrine ; Organ Size ; Plasma ; Rats ; Rats, Inbred SHR*

While phosphodiesterase type 5 inhibitors have been used for erectile dysfunction with acceptable safety profile, they can induce orthostatic hypotension in patients taking antihypertensive drugs with blood pressure lowering effect. This study evaluated the hemodynamic effects of 100 mg mirodenafil in hypertensive patients taking an amlodipine. Thirteen hypertensive patients who were taking 5 or 10 mg of amlodipine once daily participated in a randomized, double-blind, placebo-controlled, crossover study. A single oral dose of mirodenafil 100 mg or placebo was administered at 4.5 hour after administration of amlodipine. The maximal change in systolic and diastolic blood pressure (ΔmaxSBP and ΔmaxDBP) and pulse rate (ΔmaxPR) were compared between mirodenafil and placebo periods. Twelve patients completed this study and were included analysis. The values of ΔmaxPR in standing and supine position were significantly greater in the mirodenafil period (13.25±7.12 and 11.17±4.86 beats/minute) when compared to the placebo (8.50±4.72 and 6.58±3.90 beats/minute). The ΔmaxSBP and ΔmaxDBP in standing position appeared to be lower in the mirodenafil period, but they were not statistically different from those in the placebo period (ΔmaxSBP = -7.42±5.6 vs -4.42±5.37 mmHg and ΔmaxDBP = -7.17±5.72 vs -3.50±3.37 mmHg). Both ΔmaxSBP and ΔmaxDBP in standing and supine position were not significantly different between mirodenafil and placebo. This study demonstrated that mirodenafil exerted minimal hemodynamic effects in the patients taking amlodipine, that is unlikely associated with a clinically significant hypotensive event.
Amlodipine* ; Antihypertensive Agents ; Blood Pressure ; Cross-Over Studies ; Erectile Dysfunction ; Heart Rate ; Hemodynamics* ; Humans ; Hypotension, Orthostatic ; Male ; Phosphodiesterase 5 Inhibitors ; Posture ; Supine Position