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1.
Rev Med Chil ; 147(7): 932-934, 2019 Jul.
Artículo en Español | MEDLINE | ID: mdl-31859993

RESUMEN

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.


Asunto(s)
Acenocumarol/efectos adversos , Amlodipino/efectos adversos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Metformina/efectos adversos , Protrombina/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Acenocumarol/administración & dosificación , Administración Intravenosa , Anciano de 80 o más Años , Amlodipino/administración & dosificación , Humanos , Infarto de la Arteria Cerebral Media/etiología , Masculino , Metformina/administración & dosificación , Accidente Cerebrovascular/etiología , Tomografía Computarizada por Rayos X
2.
N Engl J Med ; 381(12): 1114-1123, 2019 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-31532959

RESUMEN

BACKGROUND: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called "polypills") containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low. METHODS: We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months. RESULTS: The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, -7 mm Hg; 95% confidence interval [CI], -12 to -2; P = 0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, -11 mg per deciliter; 95% CI, -18 to -5; P<0.001). CONCLUSIONS: A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.).


Asunto(s)
Antihipertensivos/administración & dosificación , Combinación de Medicamentos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Área sin Atención Médica , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Alabama , Amlodipino/administración & dosificación , Atorvastatina/administración & dosificación , LDL-Colesterol/sangre , Centros Comunitarios de Salud , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Hipercolesterolemia/sangre , Hipercolesterolemia/complicaciones , Hipertensión/complicaciones , Losartán/administración & dosificación , Masculino , Persona de Mediana Edad
3.
Pregnancy Hypertens ; 17: 209-215, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31487643

RESUMEN

OBJECTIVE: This study aimed to evaluate the relationship between endogenous CYP3A markers and plasma amlodipine (AML) exposure and metabolism parameters in early postpartum and non-peripartum women. METHODS: Twenty-four AML-treated early postpartum women with hypertensive disorders of pregnancy and 30 non-peripartum women with essential hypertension were enrolled. Blood samples for determination of CYP3A markers including total cholesterol-adjusted 4ß-hydroxycholesterol (4ß-OHC/TC), 25-hydroxyvitamin D (25-OHD), and AML and its metabolites in plasma were collected at 24 h after the AML treatment. RESULTS: The plasma 4ß-OHC/TC in postpartum women was higher than that in non-peripartum women, while the plasma 25-OHD was lower. The postpartum women had a lower plasma AML concentration and its metabolic ratio was higher. The plasma 4ß-OHC/TC decreased as the number of days post-delivery increased. The plasma AML concentration increased as the number of days post-delivery increased, while the metabolic ratio of AML declined slightly. Tendency toward negative correlations between the plasma 4ß-OHC/TC but not 25-OHD, and AML concentration were observed in both postpartum and non-peripartum women. In both groups, the plasma 4ß-OHC/TC was correlated with the metabolic ratio of AML. CONCLUSIONS: The early postpartum women had higher plasma 4ß-OHC and AML metabolism. The plasma 4ß-OHC had positive relationships with amlodipine metabolism in both women groups. AML metabolism and plasma 4ß-OHC may be useful as CYP3A markers in early postpartum and non-peripartum women.


Asunto(s)
Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Citocromo P-450 CYP3A/sangre , Hipertensión/tratamiento farmacológico , Preeclampsia/tratamiento farmacológico , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Hipertensión/sangre , Persona de Mediana Edad , Periodo Periparto , Preeclampsia/sangre , Embarazo , Complicaciones Cardiovasculares del Embarazo/sangre , Atención Prenatal , Adulto Joven
4.
Int J Clin Pharmacol Ther ; 57(12): 612-622, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31549624

RESUMEN

CONTEXT: A fixed-dose combination (FDC) tablet of amlodipine and rosuvastatin was recently developed for the treatment of concomitant hypertension and dyslipidemia and is anticipated to improve medication compliance. OBJECTIVE: This study was performed to compare the single-dose pharmacokinetic properties and safety of DP-R212 (FDC of amlodipine and rosuvastatin) to those of each agent co-administered in healthy Korean subjects. MATERIALS AND METHODS: A total of 36 healthy Korean subjects were enrolled in this randomized, open-label, single-dose, two-treatment, two-way crossover study. During each treatment period, subjects received the test drug (FDC tablet containing amlodipine and rosuvastatin) or reference drugs (individual tablets). Plasma samples were collected pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours post-dose. Safety was assessed by the evaluation of adverse events (AEs), laboratory assessments, 12-lead electrocardiograms (ECGs), physical examinations, and vital sign measurements. RESULTS: The 90% confidence intervals (CIs) of the geometric least-square mean ratios of AUClast and Cmax were 0.9796 - 1.0590 and 1.0135 - 1.0981 for amlodipine, and 0.9156 - 1.0490 and 0.8400 - 1.0306 for rosuvastatin, respectively. All AEs were of mild to moderate intensity, and no significant difference was observed in the incidence of AEs between the treatments. Moreover, the pharmacokinetic properties of the test and reference drugs were bioequivalent to each other, satisfying the regulatory criteria (0.8 - 1.25). DISCUSSION AND CONCLUSION: Both drugs were safe and well tolerated, and the pharmacokinetic profiles were comparable between the treatments.


Asunto(s)
Amlodipino/administración & dosificación , Rosuvastatina Cálcica/administración & dosificación , Administración Oral , Amlodipino/farmacocinética , Área Bajo la Curva , Estudios Cruzados , Combinación de Medicamentos , Quimioterapia Combinada , Voluntarios Sanos , Humanos , República de Corea , Rosuvastatina Cálcica/farmacocinética , Comprimidos , Equivalencia Terapéutica
5.
Drug Des Devel Ther ; 13: 2427-2436, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31413542

RESUMEN

Background: Mortality rates increase due to iron deposition in the cardiac muscles of thalassemia major (TM) patients. Iron overload cardiomyopathy could be treated with a combination therapy of an iron chelator and an L-type calcium channel blocker. We designed a randomized controlled study to assess the potential of amlodipine, alongside chelation, in reducing myocardial iron concentration in TM patients compared with a placebo. Objectives: This study aims to estimate the change in myocardial iron concentration (MIC) determined by magnetic resonance imaging after 6 months of treatment with amlodipine, as well as measuring the changes in the secondary outcomes (liver iron concentration (LIC), serum ferritin level (SF), and left ventricle ejection fraction (LVEF)) of study participants. Methods: A single, randomized, placebo-controlled trial was performed in 40 ß-Thalassemia major patients aged between 6 and 20 years old, who received either oral amlodipine 2.5-5 mg/day or a placebo, in addition to a Deferasirox chelation regimen in a 1:1 allocation ratio. Results: After 6 months, a significant reduction was noted in the MIC of patients receiving amlodipine (n=20), compared with the patients receiving the placebo (n=20). At baseline, the mean was 0.76±0.11 mg/g dry weight, while at 6 months, the mean was 0.51±0.07 mg/g dry weight (p<0.001). Also, there was a significant change in the myocardial T2* after 6 months; the amlodipine increased the myocardial T2* from 40.63±5.45 ms at baseline to 43.25±5.35 ms (p<0.001). However, amlodipine did not significantly affect the secondary outcomes by the end of the study. Conclusion: The addition of amlodipine to the standard chelation therapy in transfusion-dependent thalassemia major patients improves myocardial iron overload without increasing the adverse effects.


Asunto(s)
Amlodipino/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Amlodipino/administración & dosificación , Bloqueadores de los Canales de Calcio/administración & dosificación , Niño , Femenino , Humanos , Hierro/análisis , Quelantes del Hierro/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Adulto Joven
6.
Expert Opin Drug Metab Toxicol ; 15(9): 687-695, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31359804

RESUMEN

Introduction: S-amlodipine is main anti-hypertensive active enantiomer of amlodipine. Bisoprolol is a ß-blocker particularly suitable for hypertensive patients with sinus tachycardia. We evaluated the pharmacokinetic interaction between S-amlodipine and bisoprolol in healthy Chinese subjects. Areas covered: Thirty-two subjects were randomly divided into two equal groups. Subjects in group A were administered S-amlodipine 5 mg for 10 days followed by S-amlodipine 5 mg plus bisoprolol 5 mg for 7 days. Subjects in group B were administered bisoprolol 5 mg for 7 days, followed by S-amlodipine 5 mg plus bisoprolol 5 mg for 10 days. Blood samples were collected for evaluation of pharmacokinetic interaction. Tolerability was evaluated by interview, vital signs, 12-lead ECGs, physical examination, and clinical laboratory tests. Expert opinion: The geometric mean ratio (90% CI) for amlodipine AUCτ,ss and Css-max during the monotherapy and combination therapy periods were 1.0389 (0.9879, 1.0926) and 1.0213 (0.9556, 1.0915). For bisoprolol, it was 1.0193 (0.9834, 1.0566) and 0.9989 (0.9133, 1.0925). Most adverse events were mild-moderate. There was high incidence of elevated alanine aminotransferase, aspartate aminotransferase, and triglyceride.This study found no pharmacokinetic interaction between S-amlodipine and bisoprolol. Alanine aminotransferase, aspartate aminotransferase, and triglycerides should be closely monitored.


Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Bisoprolol/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Adulto , Amlodipino/efectos adversos , Amlodipino/farmacocinética , Antihipertensivos/efectos adversos , Antihipertensivos/farmacocinética , Área Bajo la Curva , Grupo de Ascendencia Continental Asiática , Bisoprolol/efectos adversos , Bisoprolol/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Persona de Mediana Edad , Estereoisomerismo , Transaminasas/sangre , Triglicéridos/sangre , Adulto Joven
7.
Rev Cardiovasc Med ; 20(2): 91-98, 2019 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-31345001

RESUMEN

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Hipertensión/tratamiento farmacológico , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Cronoterapia de Medicamentos , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
8.
Basic Clin Pharmacol Toxicol ; 125(4): 345-352, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31058419

RESUMEN

The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUCτ , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUCτ , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUCτ , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.


Asunto(s)
Amlodipino/farmacocinética , Antihipertensivos/farmacocinética , Hemodinámica/efectos de los fármacos , Losartán/farmacocinética , Administración Oral , Adulto , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/farmacocinética , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Voluntarios Sanos , Humanos , Hipertensión/tratamiento farmacológico , Losartán/administración & dosificación , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
9.
Pharm Biol ; 57(1): 306-309, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31060428

RESUMEN

CONTEXT: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease. OBJECTIVE: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague-Dawley rats (n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM). RESULTS: The results indicated that Cmax (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC(0-t) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST. DISCUSSION AND CONCLUSIONS: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb-drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.


Asunto(s)
Amlodipino/farmacocinética , Bloqueadores de los Canales de Calcio/farmacocinética , Medicamentos Herbarios Chinos/farmacología , Interacciones de Hierba-Droga , Salvia miltiorrhiza/química , Amlodipino/administración & dosificación , Amlodipino/sangre , Animales , Área Bajo la Curva , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/sangre , Cromatografía Liquida , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Masculino , Microsomas Hepáticos/metabolismo , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem
10.
Drug Des Devel Ther ; 13: 991-997, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31114155

RESUMEN

Objective: The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of a fixed dose combination (FDC) formulation and co-administration of amlodipine, olmesartan, and rosuvastatin. Materials and methods: This study was an open-label, randomized, cross-over design conducted in healthy male volunteers. All subjects received either a single FDC tablet containing amlodipine 10 mg/olmesartan 40 mg/rosuvastatin 20 mg, or were co-administered an FDC tablet containing amlodipine 10 mg/olmesartan 40 mg and a tablet containing rosuvastatin 20 mg, for each period, with 14-day washout periods. Plasma concentrations of amlodipine, olmesartan, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was evaluated by measuring vital signs, clinical laboratory parameters, physical examinations, and medical interviews. Results: Sixty-four subjects were enrolled, and 54 completed the study. The geometric mean ratios and 90% CI for the maximum plasma concentration (Cmax) and area under the curve from time zero to the last sampling time (AUCt) were 1.0716 (1.0369,1.1074) and 1.0497 (1.0243,1.0757) for amlodipine, 1.0396 (0.9818,1.1009) and 1.0138 (0.9716,1.0578) for olmesartan, and 1.0257 (0.9433,1.1152) and 1.0043 (0.9453,1.0669) for rosuvastatin. Fourteen cases of adverse events occurred in 12 subjects. There was no statistically significant clinical difference between the formulation groups. Conclusion: The 90% CI of the primary PK parameters were within the acceptance bioequivalence criteria, which is ln (0.8) and ln (1.25). These results indicate that the FDC formulation and co-administration of amlodipine, olmesartan and rosuvastatin are pharmacokinetically bioequivalent and have similar safety profiles.


Asunto(s)
Amlodipino/administración & dosificación , Amlodipino/farmacocinética , Imidazoles/administración & dosificación , Imidazoles/farmacocinética , Rosuvastatina Cálcica/administración & dosificación , Rosuvastatina Cálcica/farmacocinética , Tetrazoles/administración & dosificación , Tetrazoles/farmacocinética , Adulto , Amlodipino/sangre , Cromatografía Liquida , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Voluntarios Sanos , Humanos , Imidazoles/sangre , Masculino , Persona de Mediana Edad , Estructura Molecular , Rosuvastatina Cálcica/sangre , Relación Estructura-Actividad , Espectrometría de Masas en Tándem , Tetrazoles/sangre , Adulto Joven
11.
BMJ Case Rep ; 12(5)2019 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-31142490

RESUMEN

Drug-induced gingival overgrowth is a condition caused by side effects of treatment with one of three types of drugs: phenytoin (used in epilepsy treatment), cyclosporine A (used in transplantology after allogenic organ transplants) and calcium channel blockers (used in the treatment of hypertension). Gingival overgrowth leads to inflammation within the gums and periodontium and can amplify the existing periodontal disease leading to tooth loss. Patients who have undergone kidney transplant are given immunosuppressants to prevent transplant rejection and mostly it is accompanied with calcium channel blockers to treat hypertension associated with kidney transplant. This article reports a case of recent gingival enlargement associated with cyclosporine A and amlodipine given to a kidney transplant patient from the past 11 years.


Asunto(s)
Amlodipino/efectos adversos , Ciclosporina/efectos adversos , Sobrecrecimiento Gingival/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón , Adulto , Amlodipino/administración & dosificación , Quimioterapia Combinada , Humanos , Masculino , Ácido Micofenólico/efectos adversos
12.
BMJ Case Rep ; 12(4)2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-30992286

RESUMEN

Nephrotic range proteinuria and metabolic alkalosis are unusual findings in large vessel vasculitis. In this case, renovascular hypertension with unilateral renal artery stenosis in Takayasu arteritis was complicated by nephrotic range proteinuria. Symptoms resolved after angioplasty, although non-nephrotic proteinuria persisted. The renal pathology of Takayasu arteritis included focal glomerulosclerosis.


Asunto(s)
Alcalosis/etiología , Glomeruloesclerosis Focal y Segmentaria/etiología , Hipertensión Renovascular/complicaciones , Arteritis de Takayasu/complicaciones , Adolescente , Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Femenino , Cefalea/etiología , Humanos , Hipertensión Renovascular/diagnóstico , Hipertensión Renovascular/tratamiento farmacológico , Nicardipino/administración & dosificación , Proteinuria/etiología
13.
Indian Heart J ; 71(1): 32-38, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31000180

RESUMEN

BACKGROUND: Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard. OBJECTIVE: This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers. METHODS AND RESULTS: Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at tmax = 4 h in WBV at shear rates of 0.512 s-1 (p < 0.005), WBV at shear rates of 5.26 s-1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time. CONCLUSIONS: Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.


Asunto(s)
Amlodipino/administración & dosificación , Viscosidad Sanguínea/efectos de los fármacos , Edema/sangre , Agregación Eritrocitaria/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/etiología , Voluntarios Sanos , Hematócrito , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Masculino , Método Simple Ciego , Resultado del Tratamiento , Adulto Joven
14.
Am J Cardiovasc Drugs ; 19(3): 313-323, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30919249

RESUMEN

BACKGROUND: Angiotensin-converting enzyme inhibitors and calcium channel blockers in combination are widely recommended in hypertension guidelines. The advantages of single-pill combinations (SPCs) are increasingly recognized, so a dosage-adapted combination of perindopril and amlodipine was developed for the initial management of hypertension. OBJECTIVE: This randomized trial evaluated the blood pressure (BP)-lowering efficacy of four incremental doses of perindopril/amlodipine SPC in adults with mild-to-severe hypertension. METHODS: Eligible patients (N = 1617) were randomized to SPC perindopril 3.5 mg/amlodipine 2.5 mg (i.e., 3.5/2.5 mg) daily, uptitrating as required on a monthly basis up to 14/10 mg until BP < 140/90 mmHg (< 130/80 mmHg in patients with diabetes). The primary endpoint (proportion with controlled BP at each uptitrated dose) was evaluated at 6 months, and safety was evaluated at 9 months; 24-h ambulatory BP measurement and BP variability were also investigated. Control-arm participants (n = 1653) were randomized to irbesartan 150 mg daily, uptitrating over 3 months to irbesartan/hydrochlorothiazide 300/25 mg. RESULTS: Significant increases in BP control were observed with each dosage increment of perindopril/amlodipine, which was well tolerated, rising from 21% (3.5/2.5 mg) to 30% (7/5 mg), 37% (14/5 mg), and 42% (14/10 mg) after 1, 2, 3, and 6 months, respectively. Reductions in mean systolic and diastolic BP occurred with each incremental dose of perindopril/amlodipine. After 6 months, mean BP had fallen by 24.8/10.8 mmHg. Irbesartan-based therapy reduced clinic and 24-h BP similarly to perindopril/amlodipine, but perindopril/amlodipine reduced BP variability more in comparison. CONCLUSIONS: Incremental uptitration with dosage-adapted perindopril/amlodipine SPC is a safe and effective strategy for managing hypertension. TRIAL REGISTRATION: EudraCT (No. 2006-005799-42).


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Perindopril/administración & dosificación , Anciano , Amlodipino/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Perindopril/efectos adversos , Índice de Severidad de la Enfermedad
15.
N Engl J Med ; 380(25): 2429-2439, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-30883050

RESUMEN

BACKGROUND: The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS: In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or was taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS: The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, -3.14 mm Hg; 95% confidence interval [CI], -5.90 to -0.38; P = 0.03; and -3.00 mm Hg; 95% CI, -5.8 to -0.20; P = 0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was -0.14 mm Hg (95% CI, -2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS: These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months. (Funded by GlaxoSmithKline Africa Noncommunicable Disease Open Lab; CREOLE ClinicalTrials.gov number, NCT02742467.).


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Perindopril/administración & dosificación , Adulto , África del Sur del Sahara , Grupo de Ascendencia Continental Africana , Anciano , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Hidroclorotiazida/efectos adversos , Hipertensión/etnología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Perindopril/efectos adversos , Método Simple Ciego
16.
Clin Drug Investig ; 39(4): 385-393, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30790132

RESUMEN

BACKGROUND: Despite the overwhelming evidence and the established benefits of antihypertensive treatment, adherence to treatment remains low. OBJECTIVE: To assess the adherence to treatment with a perindopril/indapamide/amlodipine single-pill combination (SPC), its effectiveness on blood pressure (BP) reduction, as well as the safety and tolerability of this SPC over a 4-month treatment period. METHODS: This multicenter, non-interventional study prospectively included 2285 hypertensive patients on perindopril/indapamide/amlodipine SPC. The data were recorded at baseline, 1 month, and 4 months. RESULTS: Of the 2285 hypertensive patients included in the study, 50.5% were at "high/very high risk". Mean systolic (SBP)/diastolic (DBP) decreased from 162.3 ± 13.3/93.1 ± 9.3 mmHg at baseline to 129.7 ± 8.3/78.6 ± 7.1 mmHg at 4 months (p < 0.001). Patients with higher baseline BP levels showed greater BP reduction. Patients with hypertension stages 1, 2, and 3 showed mean SBP/DBP reductions of 21.5/10.4 mmHg, 34.2/14.7 mmHg, and 51.2/22.5 mmHg, respectively, at study end (p < 0.001). Only 26 patients (1.1%) prematurely discontinued treatment (0.58% due to an adverse reaction or event). CONCLUSIONS: Perindopril/indapamide/amlodipine SPC decreased BP levels rapidly and significantly. The degree of BP reduction was associated with the severity of hypertension and/or with total cardiovascular risk at baseline. Simplifying the drug regimen by using this SPC improved adherence and showed excellent tolerability.


Asunto(s)
Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Indapamida/administración & dosificación , Cumplimiento de la Medicación , Perindopril/administración & dosificación , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Combinación de Medicamentos , Femenino , Grecia/epidemiología , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos
17.
Drug Dev Ind Pharm ; 45(4): 669-682, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30633579

RESUMEN

OBJECTIVE: Innovation in material science has made it possible to fabricate a pharmaceutical material of modifiable characteristics and utility, in delivering therapeutics at a sustained/controlled rate. The objective of this study is to design and optimize the controlled release transdermal films of S-Amlodipine besylate by intercalating hydrophilic and hydrophobic polymers. METHODS: 3(2) factorial design and response surface methodology was utilized to prepare formulations by intercalating the varied concentration of polymers(A) and penetration enhancer(B) in solvent. The effect of these independent factors on drug release and flux was investigated to substantiate the ex-vivo, stability and histological findings of the study. RESULTS: FTIR, DSC revealed the compatibility of drug with polymers; however, the semicrystallinity in drug was observed under PXRD. SEM micrographs showed homogeneous dispersion and entanglement of drug throughout the matrix. Results from the permeation study suggested the significant effect of factors on the ex vivo permeation of drug. It was observed that drug release was found to be increased with an increase in hydrophilic polymer concentration and PE. The formulations having polymers (EC:PVPK-30) at 7:3 showed maximum drug release with highest flux (102.60 ± 1.12 µg/cm2/h) and permeability coefficient (32.78 ± 1.38 cm/h). Significant effect of PE on lipid and protein framework of the skin was also observed which is responsible for increased permeation. The optimized formulation was found to be stable and showed no-sign of localized reactions, indicating safety and compatibility with the skin. CONCLUSION: Thus, results indicated that the prepared intercalated transdermal matrix can be a promising nonoral carrier to deliver effective amounts of drug.


Asunto(s)
Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Diseño de Fármacos , Parche Transdérmico , Administración Cutánea , Amlodipino/administración & dosificación , Amlodipino/farmacocinética , Animales , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacocinética , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos , Excipientes/química , Interacciones Hidrofóbicas e Hidrofílicas , Permeabilidad , Polímeros/química , Ratas , Ratas Wistar , Piel/efectos de los fármacos , Piel/metabolismo , Absorción Cutánea/efectos de los fármacos
18.
Clin Ther ; 41(2): 233-248.e9, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30665829

RESUMEN

PURPOSE: Fixed-dose combination therapy with telmisartan, amlodipine, and rosuvastatin is needed in patients with hypertension and dyslipidemia for better adherence and cost-effectiveness than free-equivalent combination therapies. This study aimed to compare the efficacy and safety of combination therapy with telmisartan, amlodipine, and rosuvastatin versus telmisartan plus amlodipine or telmisartan plus rosuvastatin in patients with hypertension and dyslipidemia. METHODS: The Jeil Telmisartan, Amlodipine, and Rosuvastatin Randomized Clinical Trial (J-TAROS-RCT) was an 8-week, multicenter, randomized, double-blind, parallel, Phase III clinical trial conducted at 9 hospitals in Korea. After a run-in period of >4 weeks, patients who fulfilled the criteria of the National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for randomization to receive 1 of 3 treatments for 8 weeks: (1) telmisartan/amlodipine 80 mg/10 mg plus rosuvastatin 20 mg, (2) telmisartan/amlodipine 80 mg/10 mg, or (3) telmisartan 80 mg plus rosuvastatin 20 mg. The primary end point was efficacy evaluation of combination therapy with telmisartan/amlodipine/rosuvastatin by comparing the change in mean sitting systolic blood pressure (msSBP) and mean percentage change in LDL-C from baseline after 8 weeks of treatment. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: Among 148 patients, the changes in msSBP from baseline after 8 weeks of treatment were a mean (SD) of -24.41 (2.38) versus -9.31 (2.36) mm Hg in the telmisartan/amlodipine/rosuvastatin and telmisartan/rosuvastatin groups, respectively. Significantly more participants achieved the target BP at week 8 in the telmisartan/amlodipine/rosuvastatin group (41 patients [87.2%]) than in the telmisartan/rosuvastatin group (24 [50.0%], P < 0.001). The changes in mean (SD) LDL-C at 8 weeks compared with baseline values were -57.59% (11.59%) versus 6.08% (20.98%) in the telmisartan/amlodipine/rosuvastatin and telmisartan/amlodipine groups, respectively. The percentages of patients who achieved the target LDL-C according to their risk factors after 8 weeks of treatment were 97.87% vs 6.12% in the telmisartan/amlodipine/rosuvastatin and the telmisartan/amlodipine groups (P < 0.0001), respectively. No significant differences were found in the incidence of overall AEs and adverse drug reactions, and serious AEs were comparable among 3 groups. IMPLICATIONS: Fixed-dose combinations of telmisartan, amlodipine, and rosuvastatin decreased BP and LDL-C in patients with hypertension and dyslipidemia. The safety and tolerability profiles of fixed-dose telmisartan, amlodipine, and rosuvastatin combination therapy were comparable with those of telmisartan plus amlodipine or telmisartan plus rosuvastatin. ClinicalTrials.gov identifier: NCT03088254.


Asunto(s)
Amlodipino/administración & dosificación , Anticolesterolemiantes/administración & dosificación , Antihipertensivos/administración & dosificación , Dislipidemias/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Rosuvastatina Cálcica/administración & dosificación , Telmisartán/administración & dosificación , Anciano , Amlodipino/efectos adversos , Anticolesterolemiantes/efectos adversos , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Rosuvastatina Cálcica/efectos adversos , Telmisartán/efectos adversos
19.
Am J Med ; 132(2): 172-174, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30240679

RESUMEN

The US Food and Drug Administration recently granted an approved indication for the first fixed-dose combination antihypertensive (amlodipine) and nonsteroidal anti-inflammatory drug (celecoxib) for treatment of comorbid hypertension and osteoarthritis. This review summarizes available data on this combination product, to be marketed as Consensi (Kitov Pharmaceuticals, Ltd, Tel Aviv, Israel), and discusses its potential place in therapy.


Asunto(s)
Amlodipino/uso terapéutico , Celecoxib/uso terapéutico , Hipertensión/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Amlodipino/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Celecoxib/administración & dosificación , Humanos
20.
Heart Vessels ; 34(4): 698-710, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30406819

RESUMEN

There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.


Asunto(s)
Amlodipino/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/complicaciones , Hipertensión Esencial/tratamiento farmacológico , Anciano , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , Bloqueadores de los Canales de Calcio/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Hipertensión Esencial/complicaciones , Hipertensión Esencial/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Resultado del Tratamiento
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