PMID- 27137712
OWN - NLM
STAT- MEDLINE
DCOM- 20180122
LR  - 20220311
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 4
IP  - 6
DP  - 2015 Nov
TI  - Pharmacokinetic drug-drug interaction assessment between LCZ696, an angiotensin 
      receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or 
      carvedilol.
PG  - 407-17
LID - 10.1002/cpdd.183 [doi]
AB  - LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor in 
      development for treatments of hypertension and heart failure indications. In 3 
      separate studies, pharmacokinetic drug-drug interactions (DDIs) potential was 
      assessed when LCZ696 was coadministered with hydrochlorothiazide (HCTZ), 
      amlodipine, or carvedilol. The studies used a open-label, single-sequence, 
      3-period, crossover design in healthy subjects. Blood samples were collected to 
      determine the pharmacokinetic parameters of LCZ696 analytes (AHU377, LBQ657, and 
      valsartan), HCTZ, amlodipine, or carvedilol (R[+]- and S[-]-carvedilol) for 
      statistical analysis. When coadministered LCZ696 with HCTZ, the 90% CIs of the 
      geometric mean ratios of AUCtau,ss of HCTZ and that of LBQ657 were within a 
      0.80-1.25 interval, whereas HCTZ Cmax,ss decreased by 26%, LBQ657 Cmax,ss 
      increased by 19%, and the AUCtau,ss and Cmax,ss of valsartan increased by 14% and 
      16%, respectively. Pharmacokinetics of amlodipine, R(+)- and S(-)-carvedilol, or 
      LBQ657 were not altered after coadministration of LCZ696 with amlodipine or 
      carvedilol. Coadministration of LCZ696 400 mg once daily (qd) with HCTZ 25 mg qd, 
      amlodipine 10 mg qd, or carvedilol 25 mg twice a day (bid) had no clinically 
      relevant pharmacokinetic drug-drug interactions. LCZ696, HCTZ, amlodipine, and 
      carvedilol were safe and well tolerated when given alone or concomitantly in the 
      investigated studies.
CI  - (c) 2015, The American College of Clinical Pharmacology.
FAU - Hsiao, Hsiu-Ling
AU  - Hsiao HL
AD  - Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals 
      Corporation, East Hanover, NJ, USA.
FAU - Langenickel, Thomas Heiko
AU  - Langenickel TH
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Greeley, Michael
AU  - Greeley M
AD  - Oncology Clinical Pharmacology, Novartis Pharmaceuticals Corporation, East 
      Hanover, NJ, USA.
FAU - Roberts, John
AU  - Roberts J
AD  - Oncology Clinical Pharmacology, Novartis Pharmaceuticals Corporation, East 
      Hanover, NJ, USA.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals 
      Corporation, East Hanover, NJ, USA.
FAU - Pal, Parasar
AU  - Pal P
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
FAU - Rebello, Sam
AU  - Rebello S
AD  - Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals 
      Corporation, East Hanover, NJ, USA.
FAU - Rajman, Iris
AU  - Rajman I
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Sunkara, Gangadhar
AU  - Sunkara G
AD  - Novartis Institutes for Biomedical Research, Novartis Pharmaceuticals 
      Corporation, East Hanover, NJ, USA.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20150506
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Aminobutyrates)
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Carbazoles)
RN  - 0 (Diuretics)
RN  - 0 (Drug Combinations)
RN  - 0 (Propanolamines)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Tetrazoles)
RN  - 0J48LPH2TH (Hydrochlorothiazide)
RN  - 0K47UL67F2 (Carvedilol)
RN  - 1J444QC288 (Amlodipine)
RN  - 80M03YXJ7I (Valsartan)
RN  - EC 3.4.24.11 (Neprilysin)
RN  - WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
SB  - IM
MH  - Administration, Oral
MH  - Adrenergic beta-Antagonists/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Adult
MH  - Aminobutyrates/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Amlodipine/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Angiotensin Receptor Antagonists/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Antihypertensive Agents/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Arizona
MH  - Biphenyl Compounds
MH  - Calcium Channel Blockers/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Carbazoles/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Carvedilol
MH  - Cross-Over Studies
MH  - Diuretics/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Drug Therapy, Combination
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Hydrochlorothiazide/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Models, Biological
MH  - Neprilysin/*antagonists & inhibitors/metabolism
MH  - Propanolamines/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Protease Inhibitors/administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Tetrazoles/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Valsartan
OTO - NOTNLM
OT  - LCZ696
OT  - amlodipine
OT  - carvedilol
OT  - hydrochlorothiazide
OT  - pharmacokinetic drug-drug interaction
EDAT- 2016/05/04 06:00
MHDA- 2016/05/04 06:01
CRDT- 2016/05/04 06:00
PHST- 2014/07/31 00:00 [received]
PHST- 2015/02/05 00:00 [accepted]
PHST- 2016/05/04 06:00 [entrez]
PHST- 2016/05/04 06:00 [pubmed]
PHST- 2016/05/04 06:01 [medline]
AID - 10.1002/cpdd.183 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2015 Nov;4(6):407-17. doi: 10.1002/cpdd.183. Epub 2015 
      May 6.