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Rongzhong Huang, Yuxing Feng, Ying Wang, Xiaoxia Qin, Narayan Dhruvaraj Melgiri, Yang Sun, Xingsheng Li
BACKGROUND: Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria...
2017: PloS One
S-W Chang, C W McDonough, Y Gong, T A Johnson, T Tsunoda, E R Gamazon, M A Perera, A Takahashi, T Tanaka, M Kubo, C J Pepine, J A Johnson, R M Cooper-DeHoff
We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a β-blocker-based strategy (β-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls)...
September 27, 2016: Pharmacogenomics Journal
Islam Y Elgendy, Anthony A Bavry, Yan Gong, Eileen M Handberg, Rhonda M Cooper-DeHoff, Carl J Pepine
The dyad of hypertension and coronary artery disease is prevalent; however, data on systolic blood pressure (SBP) control and long-term all-cause mortality are lacking. Using extended follow-up data from the US cohort of the International Verapamil (SR)/Trandolapril Study (mean 11.6 years), subjects were categorized by age at enrollment (50 to <60 and ≥60 years). Cox proportional adjusted hazard ratios (HRs) were constructed for time to all-cause mortality according to achieved mean SBP. In those 50 to <60 years and using a referent SBP of <130 mm Hg, an achieved SBP of 130 to 140 mm Hg was associated with a similar risk of mortality (HR, 1...
November 2016: Hypertension
Sungha Park, Kazuomi Kario, Chang Gyu Park, Qi Fang Huang, Hao Min Cheng, Satoshi Hoshide, Ji Guang Wang, Chen Huan Chen
Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despite the significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality...
November 2016: Yonsei Medical Journal
Shanta Bhar, Mucheli M V Ramana
With reference to challenges in developing varied and exceedingly complex scaffolds expeditiously through atom economy, domino reactions have assumed a significant role in several transformative endeavors towards established pharmaceuticals and new chemical entities across diverse therapeutic classes such as HIV integrase inhibitors, DPP4 [dipeptidyl peptidase IV] inhibitors, GSK-3 (Glycogen Synthase Kinase 3) inhibitors, neoplastic drugs and microtubule antagonists. The very large chemical space of Domino Reactions can be leveraged for the design strategy of drugs and drug-like candidates with leading examples like Indinavir (Crixivan), Trandolapril (Mavik), Biyouyanagin A, endo pyrrolizidinone diastereomer [GSK] and several others...
August 19, 2016: Current Drug Discovery Technologies
Scott J Denardo, Yan Gong, Rhonda M Cooper-DeHoff, Csaba Farsang, Matyas Keltai, László Szirmai, Franz H Messerli, Anthony A Bavry, Eileen M Handberg, Giuseppe Mancia, Carl J Pepine
[This corrects the article DOI: 10.1371/journal.pone.0122726.].
2016: PloS One
Steven M Smith, Tianyao Huo, Yan Gong, Eileen Handberg, Martha Gulati, C Noel Bairey Merz, Carl J Pepine, Rhonda M Cooper-DeHoff
BACKGROUND: Women are at greater risk of developing resistant hypertension (RH) than men, yet scarce data exist on RH-associated outcomes in women. We aimed to determine all-cause mortality risk associated with apparent RH (aRH) among women across the spectrum of underlying coronary disease. MATERIALS AND METHODS: We analyzed data from St. James Women Take Heart (WTH; women without coronary disease at baseline), Women's Ischemia Syndrome Evaluation (women with signs/symptoms of ischemia at baseline), and the INternational VErapamil-Trandolapril STudy (INVEST; women with coronary artery disease and hypertension at baseline), totaling 15,108 adult women with no hypertension, non-RH (blood pressure [BP] ≥140/90 mmHg on ≤2 drugs or BP <140/90 mmHg on 1-3 drugs), or aRH (BP ≥140/90 mmHg on ≥3 drugs or anyone on ≥4 drugs) at baseline...
October 2016: Journal of Women's Health
Bülent Albayrak, Erdem Cankaya, Ramazan Cetinkaya, Serkan Cerrah, Yusuf Bilen
Diabetic nephropathy (DN) is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males) with overt proteinuria and DN were included in this study...
May 2016: Saudi Journal of Kidney Diseases and Transplantation
Hao-Jie Zhu, Taimour Y Langaee, Yan Gong, Xinwen Wang, Carl J Pepine, Rhonda M Cooper-DeHoff, Julie A Johnson, John S Markowitz
PURPOSE: The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant -816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs...
June 2016: European Journal of Clinical Pharmacology
WeiPing Sun, HaiBin Zhang, JinCheng Guo, XueKun Zhang, LiXin Zhang, ChunLei Li, Ling Zhang
Heart failure is a public health problem and a great economic burden for patients and healthcare systems. Suppression of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE)-inhibitors remains the mainstay of treatment for heart failure. However, the abundance of ACE inhibitors makes it difficult for doctors to choose.We performed this network meta-analysis of ACEIs in patients with heart failure in order to address this area of uncertainty.We searched PubMed, Embase, CENTRAL, and Medline...
February 2016: Medicine (Baltimore)
E Lambert Kuhn, D Levêque, B Lioure, B Gourieux, P Bilbault
WHAT IS KNOWN AND OBJECTIVE: Ibrutinib is a recently approved oral anticancer agent with pharmacokinetics that is very sensitive to metabolic inhibition. We report a serious side effect of ibrutinib potentially attributable to interaction with the moderate CYP3A4 inhibitor verapamil. CASE DESCRIPTION: A patient with mantle cell lymphoma was admitted to our emergency department with severe diarrhoea. During a prescription review, the clinical pharmacist identified a potential drug interaction between ibrutinib and verapamil present in a branded combination product also containing trandolapril...
February 2016: Journal of Clinical Pharmacy and Therapeutics
Lubica Cibickova, Tomas Caran, Martin Dobias, Peter Ondra, Viktor Vorisek, Norbert Cibicek
Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein...
December 2015: Forensic Science International
Ana M Blázquez-Medela, Omar García-Sánchez, Yaremi Quirós, Victor Blanco-Gozalo, Laura Prieto-García, Sandra M Sancho-Martínez, Miguel Romero, Juan M Duarte, Francisco J López-Hernández, José M López-Novoa, Carlos Martínez-Salgado
Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage...
October 2015: Medicine (Baltimore)
Yan Gong, Caitrin W McDonough, Amber L Beitelshees, Nihal El Rouby, Timo P Hiltunen, Jeffrey R O'Connell, Sandosh Padmanabhan, Taimour Y Langaee, Karen Hall, Siegfried O F Schmidt, Robert W Curry, John G Gums, Kati M Donner, Kimmo K Kontula, Kent R Bailey, Eric Boerwinkle, Atsushi Takahashi, Toshihiro Tanaka, Michiaki Kubo, Arlene B Chapman, Stephen T Turner, Carl J Pepine, Rhonda M Cooper-DeHoff, Julie A Johnson
OBJECTIVE: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol. METHODS: Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n = 2114)...
November 2015: Journal of Hypertension
A A Elgarov, R M Aramisova, M A Elgarov, M A Kalmykova
AIM: To estimate effectiveness and safety of pharmacotherapy in vehicle drivers with arterial hypertension (AH). MATERIALS AND METHODS: 432 patients with grade I-III AH including 82 with cardiovascular complications largely of II and III grade were under observation during 2.5-4 months using clinical and instrumental methods (24hr AP & ECG monitoring) as well as psychophysiological testing (PPT). RESULTS: Ramipril and atenolol were efficient in 77...
2015: Klinicheskaia Meditsina
L Červenka, V Melenovský, Z Husková, A Sporková, M Bürgelová, P Škaroupková, S H Hwang, B D Hammock, J D Imig, J Sadowski
The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment...
2015: Physiological Research
Luděk Červenka, Vojtěch Melenovský, Zuzana Husková, Petra Škaroupková, Akira Nishiyama, Janusz Sadowski
The detailed mechanisms determining the course of congestive heart failure (CHF) in hypertensive subjects with associated renal dysfunction remain unclear. In Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension, CHF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). In these rats we investigated the putative pathophysiological contribution of epoxyeicosatrienoic acids (EETs) and compared it with the role of the renin-angiotensin system (RAS)...
July 2015: Clinical and Experimental Pharmacology & Physiology
Xiaojiao Li, Chang Liu, Min Wu, Hong Zhang, Yanfu Sun, Longmei Cheng, Hong Chen, Chengjiao Liu, Lizhi Yang, Qi Zhang, Yuchen Cao, Jingkai Gu, Yanhua Ding
Trandolapril is the pro-drug of trandolaprilat, a non-sulfhydryl angiotensin-converting enzyme inhibitor. This study was designed to assess the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of single and multiple doses of trandolapril in healthy Chinese subjects. Healthy subjects (six men and six women) were randomized into a single-dose, 3 × 3 crossover study (1-2-4 mg, 2-4-1 mg, and 4-1-2 mg), and a multiple-dose study (2 mg/day, 6 days). Serial blood and urine samples were collected after drug administration and analyzed using a validated LC-MS/MS method, and the trandolapril and trandolaprilat PK parameters were obtained...
August 2016: European Journal of Drug Metabolism and Pharmacokinetics
Scott J Denardo, Yan Gong, Rhonda M Cooper-DeHoff, Csaba Farsang, Matyas Keltai, László Szirmai, Franz H Messerli, Anthony A Bavry, Eileen M Handberg, Giuseppe Mancia, Carl J Pepine
Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥ 50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies...
2015: PloS One
Leena A Al-Hawash, Ashok K Shakya, Maher L Saleem
A rapid, simple, accurate, precise, economical, robust, and stability indicating reverse phase HPLC-PDA procedure has been developed and validated for the determination of trandolapril. The trandolapril was separated isocratically on Hypersil-Gold C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of 50% acetonitrile and 50% water (containing 0.025% triethylamine, pH 3.0 ± 0.1), at 25 ± 2°C. Retention time of the drug was ~4.6 min. The eluted compounds were monitored and identified at 210 nm...
2015: International Journal of Analytical Chemistry
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