scholarly journals Pharmacokinetics and drug-drug interaction between enalapril, enalaprilat and felodipine extended release (ER) in healthy subjects

Oncotarget ◽  
2017 ◽  
Vol 8 (41) ◽  
pp. 70752-70760 ◽  
Author(s):  
Dai Li ◽  
Sumei Xu ◽  
Yulu Wang ◽  
Dan Li ◽  
Xiaomin Li ◽  
...  
2019 ◽  
Vol 12 (5) ◽  
pp. 513-518 ◽  
Author(s):  
Naoyuki Otani ◽  
Hirokazu Wakuda ◽  
Hiromitsu Imai ◽  
Masae Kuranari ◽  
Yasuyuki Ishii ◽  
...  

Author(s):  
Ana Santos ◽  
Luis Magalhães ◽  
Andreia Guimarães ◽  
Helena Gama ◽  
Paulo Magalhaes ◽  
...  

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Hsiu-Ling Hsiao ◽  
Michael Greeley ◽  
Parasar Pal ◽  
Thomas Langenickel ◽  
Gangadhar Sunkara ◽  
...  

Objective: LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) being developed for the treatment of cardiovascular diseases, including hypertension and heart failure. Ingestion of LCZ696 results in systemic exposure to AHU377 (inactive prodrug of LBQ657, a neprilysin inhibitor) and valsartan (angiotensin receptor blocker). Hydrochlorothiazide (HCTZ) is indicated as first line treatment of hypertension. Since LCZ696 and HCTZ may be co-administered for optimal blood pressure control, this study was conducted to evaluate the pharmacokinetic (PK) drug-drug interaction potential between LCZ696 and HCTZ. Methods: An open-label, three-period, single sequence study in 27 healthy subjects was conducted. In Period 1, subjects received oral HCTZ 25 mg qd x 4 days and were discharged for a 4-10 day washout. In Period 2, subjects received LCZ696 400 mg qd x 5 days, and in Period 3, HCTZ 25 mg qd + LCZ696 400 mg qd x 4 days. Serial PK samples were collected and analyzed by a validated LC-MS/MS method. PK parameters (AUCtau,ss,Cmax,ss) of LCZ696 analytes (LBQ657, valsartan) and HCTZ in plasma were determined using non-compartmental analysis, and the results were statisticallyevaluated. Results: The 90% CIs confidence intervals (CIs) for the geometric mean ratio for AUCtau,ss of HCTZ fell within the ( 0.8 - 1.25) range, while those of Cmax,ss (0.74, 0.70-0.78) fell outside the range, indicating Cmax,ss of HCTZ decreased by 26% when co-administered with LCZ696. Those for AUCtau,ss of LBQ657 fell within the range but the upper bound for Cmax,ss (1.19, 1.10-1.28) was outside the range, indicating Cmax of LBQ657 increased by 19%; the upper bound for valsartan exposures(AUCtau,ss: 1.14, 1.00-1.29; Cmax,ss: 1.16, 0.98-1.37) were above the range, indicating AUCtau,ss and Cmax,ss of valsartan increased by 14%and 16%, respectively. Conclusion: When LCZ696 400mg qd and HCTZ 25mg qd were co- administered, AUCtau,ss of HCTZ was unchanged but Cmax,ss decreased by 26%; AUCtau,ss of LBQ657 was unchanged but Cmax,ss increased by 19%; and lastly, AUCtau,ss and Cmax,ss of valsartan increased by 14%and 16%, respectively. LCZ696 400 mg qd was safe and well tolerated in healthy subjects when administered alone and in combination with HCTZ 25 mg qd.


2018 ◽  
Vol 38 (11) ◽  
pp. 1053-1060 ◽  
Author(s):  
Nao Kawaguchi ◽  
Hiroki Koshimichi ◽  
Toru Ishibashi ◽  
Toshihiro Wajima

Author(s):  
Ana Santos ◽  
João Ferreira ◽  
Helena Gama ◽  
Paulo Magalhães ◽  
Patricio Soares-Da-Silva

2016 ◽  
Vol 6 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Amit Desai ◽  
Takao Yamazaki ◽  
Albert J. Dietz ◽  
Donna Kowalski ◽  
Christopher Lademacher ◽  
...  

CHEST Journal ◽  
2020 ◽  
Vol 158 (4) ◽  
pp. A2271
Author(s):  
Luis Magalhaes ◽  
Andreia Guimaraes ◽  
Ana Santos ◽  
Helena Gama ◽  
Patricio Soares-da-Silva

2018 ◽  
Vol 84 (10) ◽  
pp. 2317-2324 ◽  
Author(s):  
Masaya Tachibana ◽  
Naotoshi Yamamura ◽  
George J. Atiee ◽  
Ching Hsu ◽  
Vance Warren ◽  
...  

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