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Pharmacology Research & Perspectives Apr 2023This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood...
This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood pressure reduction in vivo by both SynergyFinder 3.0 and probability sum test. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (0.5, 1, 2, and 4 mg/kg), telmisartan (4, 8, and 16 mg/kg), candesartan (1, 2, and 4 mg/kg), nine combinations for amlodipine and telmisartan, and nine combinations for amlodipine and candesartan. The control rats were treated by 0.5% carboxymethylcellulose sodium. Blood pressure was recorded continuously up to 6 h after administration. Both SynergyFinder 3.0 and the probability sum test were used to evaluate the synergistic action. The synergisms calculated by SynergyFinder 3.0 are consistent with the probability sum test both in two different combinations. There is an obviously synergistic interaction between amlodipine and telmisartan or candesartan. The combinations of amlodipine and telmisartan (2 + 4 and 1 + 4 mg/kg) and amlodipine and candesartan (0.5 + 4 and 2 + 1 mg/kg) might exert an optimum synergism against hypertension. Compared with the probability sum test, SynergyFinder 3.0 is more stable and reliable to analyze the synergism.
Topics: Rats; Animals; Telmisartan; Blood Pressure; Amlodipine; Antihypertensive Agents; Hypotension; Rats, Inbred SHR
PubMed: 36810974
DOI: 10.1002/prp2.1064 -
Electrophoresis Jul 2022The histidine-modified zeolitic imidazolate framework [His-ZIF-67] was prepared with the histidine, 2-methylimidazole, and Co under ambient temperature. His-ZIF-67 was...
The histidine-modified zeolitic imidazolate framework [His-ZIF-67] was prepared with the histidine, 2-methylimidazole, and Co under ambient temperature. His-ZIF-67 was bonded via a glycidyl methacrylate copolymer to the internal surface of capillary and then functionalized with the NH -β-cyclodextrin (NH -β-CD). The materials were characterized by field emission scanning electron microscopy, high-resolution transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, N adsorption-desorption isotherm, X-ray diffraction, and X-ray photoelectron spectroscopy. In comparison with the NH -β-CD@capillary, the NH -β-CD@His-ZIF-67@capillary-coated column shows significantly enhanced resolution for chiral molecules. The NH -β-CD@His-ZIF-67@capillary column achieved the baseline separation of amlodipine and metoprolol (the resolution of amlodipine: 1.70; metoprolol: 1.50) and the partial separation of atenolol and propranolol (the resolution of atenolol: 1.03; propranolol: 0.60). These were attributed to the histidine modification and the features of ZIF-67, including an excellent surface area and the abundant porosity. The pH and proportion of organic modifier in the buffer were crucial for enantioseparation performance and were evaluated in detail. The fabricated NH -β-CD@His-ZIF-67@capillary-coated column showed good stability and repeatability (relative standard deviation <6.3%). The molecular modeling with AutoDock and grand canonical ensemble was carried out to evaluate the interactions between chiral stationary phase and racemic drugs.
Topics: Amlodipine; Atenolol; Capillary Electrochromatography; Cyclodextrins; Histidine; Metoprolol; Propranolol; Stereoisomerism; Zeolites
PubMed: 35338718
DOI: 10.1002/elps.202100299 -
International Journal of Clinical... Jun 2021Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID-19.
METHODS
In this randomised clinical trial, hospitalised patients with COVID-19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30-day mortality rate and length of hospital stay.
RESULTS
The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30-day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241).
CONCLUSIONS
There was no priority in losartan or amlodipine administration in COVID-19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first-line anti-HTN medications in COVID-19.
Topics: Aged; Aged, 80 and over; Amlodipine; Antihypertensive Agents; Blood Pressure; COVID-19; Double-Blind Method; Humans; Hypertension; Losartan; Middle Aged; SARS-CoV-2; Treatment Outcome
PubMed: 33650197
DOI: 10.1111/ijcp.14124 -
Hypertension (Dallas, Tex. : 1979) Jan 2021Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of... (Meta-Analysis)
Meta-Analysis Review
Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of antihypertensive medications in patients with hypertension. Trough concentrations could possibly be used as drug-specific cutoff values in the biochemical assessment of (non-)adherence. We performed a literature review and meta-analysis of pharmacokinetic studies to determine plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan. PubMed was searched for pharmacokinetic studies up to September 2020. Eligible studies reported steady-state mean trough concentration and their variance. Pooled trough concentrations were estimated using a three-level random effects meta-analytic model. Moderator analyses were performed to explore sources of heterogeneity. One thousand three hundred eighteen potentially relevant articles were identified of which 45 were eligible for inclusion. The pooled mean trough concentration was 9.2 ng/mL (95% CI, 7.5-10.8) for amlodipine, 41.0 ng/mL (95% CI, 17.4-64.7) for hydrochlorothiazide, and 352.9 ng/mL (95% CI, 243.5-462.3) for valsartan. Substantial heterogeneity was present for all 3 pooled estimates. Moderator analyses identified dosage as a significant moderator for the pooled trough concentration of amlodipine (β=0.9; <0.05), mean age, and mean body weight for the mean trough concentration of hydrochlorothiazide (β=2.2, <0.05, respectively, β=-4.0, <0.05) and no significant moderators for valsartan. Plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan, measured with liquid chromatography-tandem mass spectrometry, are highly heterogeneous over the different studies. Use of the pooled trough concentration as a cutoff in the biochemical assessment of adherence can result in inaccurate diagnosis of (non-)adherence, which may seriously harm the patient-physician relationship, and is therefore not recommended.
Topics: Amlodipine; Antihypertensive Agents; Humans; Hydrochlorothiazide; Hypertension; Treatment Adherence and Compliance; Valsartan
PubMed: 33249865
DOI: 10.1161/HYPERTENSIONAHA.120.16061 -
Journal of the American Heart... May 2024Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by...
BACKGROUND
Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages.
METHODS AND RESULTS
Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]).
CONCLUSIONS
Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.
Topics: Humans; Amlodipine; Male; Hypercholesterolemia; Hypertension; Female; Middle Aged; Atorvastatin; Aged; Taiwan; Drug Combinations; Treatment Outcome; Antihypertensive Agents; Retrospective Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Calcium Channel Blockers; Blood Pressure; Heptanoic Acids; Pyrroles
PubMed: 38686894
DOI: 10.1161/JAHA.123.033780 -
Sudebno-meditsinskaia Ekspertiza 2022The objective of the study is to determine amlodipine assay conditions and stability in biological material. Thin layer chromatography (TLC), gas chromatography-mass...
The objective of the study is to determine amlodipine assay conditions and stability in biological material. Thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS) and UV-spectrophotometry were used for identification. Amlodipine was recovered from biomaterial by double (30 min each) infusing with acetone at the ratio of recovery solution and sample 2:1 (w/w). The purification was carried out by extraction and chromatography in a semi-preparative column with reverse-phase packing material Silasorb C-18 using acetone/water eluent (8:2). Amlodipine assay was performed by TLC [Sorbfil plates, butanol/acetone (5:5) as a mobile phase], GC-MS (HP-5 ms Ultra inert column (30 m×0.25×0.25 μm) with stationary phase of 5% phenyl-95% dimethyl polysiloxane), UV-spectrophotometry (95% ethanol as a solvent). The proposed assay method for amlodipine in biomaterial (liver tissue) is validated for linearity, selectivity, accuracy and precision. The amlodipine stability in model mixtures with liver tissue was studied. It was shown that the analyte stability in biological material decreases with increasing temperature. Amlodipine is stable at -25 °C, 0-2 °C, 8-10 °C, 18-22 °C, and 36 °C for 120, 112, 105, 91, and 77 days, respectively.
Topics: Acetone; Amlodipine; Biocompatible Materials; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Reproducibility of Results
PubMed: 35947410
DOI: 10.17116/sudmed20226504146 -
PeerJ 2023Sporotrichosis caused by is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the activity of amlodipine (AML) and...
BACKGROUND
Sporotrichosis caused by is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the activity of amlodipine (AML) and lufenuron (LUF) alone and their interaction with itraconazole (ITZ), the first-choice drug against .
METHODS
Twenty clinical isolates of from two hyperendemic regions were tested through a microdilution assay to evaluate the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AML and LUF. Checkerboard assay was performed with 10 isolates for both drug interactions with ITZ.
RESULTS
AML showed inhibitory and fungicidal activity against all isolates included, with MIC values ranging from 32 to 256 µg/mL, and MFC from 64 to 256 µg/mL. However, none of the isolates were inhibited by the highest soluble concentration of LUF (MIC >64 µg/mL for all strains). Synergic interaction of AML and LUF with ITZ occurred in 50% and 40% of the isolates tested, without any antagonistic effects.
CONCLUSION
Both repurposing drugs evaluated in our study showed a promising activity, especially in synergy with ITZ against , warranting future investigations regarding its activity.
Topics: Humans; Antifungal Agents; Amlodipine; Drug Repositioning; Itraconazole; Leukemia, Myeloid, Acute
PubMed: 38050607
DOI: 10.7717/peerj.16443 -
Current Medical Research and Opinion Jul 2023To evaluate the antihypertensive effect and safety of bisoprolol 5 mg (BISO5mg) and amlodipine 5 mg (AMLO5mg) combination in comparison to AMLO5mg in hypertensive... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of bisoprolol 5 mg plus amlodipine 5 mg in patients with hypertension uncontrolled on monotherapy with 5 mg of amlodipine, a phase III multicenter, randomized, double-blind, placebo-controlled clinical trial - the AMCOR study.
OBJECTIVE
To evaluate the antihypertensive effect and safety of bisoprolol 5 mg (BISO5mg) and amlodipine 5 mg (AMLO5mg) combination in comparison to AMLO5mg in hypertensive subjects uncontrolled with AMLO5mg.
METHODS
Phase III, prospective, randomized, double-blind, placebo-controlled, 8-week trial with parallel design (EudraCT Number: 2019-000751-13).
RESULTS
367 patients aged 57.58 ± 14.62 years were randomized to BISO5mg once daily on top of AMLO5mg ( = 181) or placebo on top of AMLO5mg ( = 186). Systolic/diastolic blood pressure (SBP/DBP) in the bisoprolol-treated group was reduced by 7.2 ± 12.74/3.95 ± 8.85 mmHg at 4 weeks (both < .0001) and by 5.5 ± 12.44/3.84 ± 9.46 mmHg at 8 weeks ( < .0001/ < .0002) compared to placebo control. Bisoprolol-treated group had lower heart rate than placebo control (difference -7.23 ± 9.84/-6.25 ± 9.26 beats per minute at 4 and 8 weeks, respectively, both < .0001). Both target SBP and DBP was achieved at 4 weeks by 62 vs. 41% ( = .0002) and at 8 weeks by 65 vs. 46% ( = .0004) of bisoprolol-treated patients and placebo group patients, respectively. SBP <140 mmHg was achieved at 4 and 8 weeks in 68 and 69% of bisoprolol-treated patients and 45 and 50% of placebo group patients, respectively. No deaths and serious adverse events were reported. Adverse events occurred in 34 bisoprolol-treated patients vs. 22 patients in the placebo group ( = .064). Bisoprolol was withdrawn due to adverse events in 7 patients, mostly ( = 4) due to asymptomatic bradycardia.
CONCLUSIONS
Addition of bisoprolol to patients uncontrolled with amlodipine monotherapy significantly improves blood pressure control. We can expect additional 7.2/3.95 mmHg SBP/DBP lowering effect by adding bisoprolol 5 mg to amlodipine 5 mg.
Topics: Humans; Amlodipine; Bisoprolol; Prospective Studies; Calcium Channel Blockers; Hypertension; Antihypertensive Agents; Blood Pressure; Double-Blind Method
PubMed: 37300442
DOI: 10.1080/03007995.2023.2223915 -
Journal of the American Heart... Aug 2019Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we...
Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we recruited 231 women with chronic hypertension, including those who received amlodipine or other antihypertensives during early pregnancy, and investigated frequencies of morphologic abnormalities in their 231 offspring. Specifically, we evaluated 48 neonates exposed to amlodipine in the first trimester (amlodipine group, Group A), 54 neonates exposed to antihypertensives other than amlodipine (other antihypertensive group, Group O), and 129 neonates not exposed to antihypertensives (no-antihypertensive group, Group N). The number of morphologic abnormalities of offspring in each group were 2 in Group A (4.2%; 95% CI, 0.51-14.25); 3 in Group O (5.6%; 95% CI, 1.16-15.39) and 6 in Group N (4.7%; 95% CI, 1.73-9.85). The odds ratio of the primary outcome comparing Group A and Group O was 0.74 (95% CI: 0.118-4.621) and Group A and Group N was 0.89 (95% CI: 0.174-4.575). Conclusions The odds of birth defects in Group A in the first trimester were not significantly different from those with or without other antihypertensives.
Topics: Abnormalities, Drug-Induced; Aged; Amlodipine; Antihypertensive Agents; Chronic Disease; Female; Follow-Up Studies; Humans; Hypertension; Infant, Newborn; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Prospective Studies
PubMed: 31345083
DOI: 10.1161/JAHA.119.012093 -
BMC Pharmacology & Toxicology Jul 2022The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects.
METHODS
A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (C) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded.
RESULTS
Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C, AUC and AUC of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80-1.25. A high-fat meal appeared to decrease the C and AUC of lisinopril. No severe adverse events were observed.
CONCLUSION
The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions.
TRIAL REGISTRATION
Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).
Topics: Amlodipine; China; Chromatography, Liquid; Fasting; Healthy Volunteers; Humans; Lisinopril; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 35794660
DOI: 10.1186/s40360-022-00590-6