Pharmacodynamic interaction between intravenous nitroglycerin and oral sacubitril/valsartan (LCZ696) in healthy subjects.
Purpose: Sacubitril/valsartan (LCZ696) and nitroglycerin share the second messenger cGMP and lower blood pressure. Given the potential for co-administration of both drugs in patients with heart failure, this study was designed to investigate the potential for a pharmacodynamic drug interaction affec...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 74; no. 9; pp. 1121 - 1131 |
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| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Sep2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=131207673&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 131207673 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Sep2018 vid: 74 iid: 9 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 131207673 131207673 131207673 10.1007/s00228-018-2509-2 131207673 ppf: 1121 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Pharmacodynamic interaction between intravenous nitroglycerin and oral sacubitril/valsartan (LCZ696) in healthy subjects. aug: au: Schuehly, Uwe Ayalasomayajula, Surya Buchbjerg, Jeppe Pal, Parasar Golor, Georg Prescott, Margaret F. Sunkara, Gangadhar Hinder, Markus Langenickel, Thomas H. affil: Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland sug: subj: Drug Interactions Nitroglycerin Administration and Dosage Valsartan Administration and Dosage Valsartan Pharmacodynamics Nitroglycerin Pharmacodynamics Heart Failure Drug Therapy Blood Pressure Drug Effects Human Randomized Controlled Trials Double-Blind Studies Crossover Design Blood Pressure Determination Heart Rate Valsartan Pharmacokinetics Systolic Pressure Drug Effects Diastolic Pressure Drug Effects Confidence Intervals Nucleotides Blood Administration, Intravenous Administration, Oral Drug Combinations ab: Purpose: Sacubitril/valsartan (LCZ696) and nitroglycerin share the second messenger cGMP and lower blood pressure. Given the potential for co-administration of both drugs in patients with heart failure, this study was designed to investigate the potential for a pharmacodynamic drug interaction affecting blood pressure.Methods: In this double-blind, placebo-controlled, randomised, crossover study, 40 healthy subjects received sacubitril/valsartan 200 mg bid (97/103 mg bid) or placebo for 5 days. Two hours after the morning dose of sacubitril/valsartan or placebo on day 5, subjects received intravenous nitroglycerin infusion at increasing doses up to 40 μg/min or placebo. Serial measurements of blood pressure (BP), heart rate, biomarkers and sacubitril/valsartan pharmacokinetics were conducted.Results: Administration of nitroglycerin alone led to a dose- and time-dependent decrease in supine systolic BP (SBP) and diastolic BP (DBP) which was similar when nitroglycerin was co-administered with sacubitril/valsartan. At the highest dose of nitroglycerin, the mean (95% CI) decrease from baseline of SBP/DBP was 19.54 (− 21.99, − 17.09)/12.38 (− 13.85, − 10.92) mmHg for nitroglycerin alone compared to 22.63 (− 25.06, − 20.21)/12.94 (− 14.38, − 11.49) mmHg when co-administered with sacubitril/valsartan. Co-administration of sacubitril/valsartan and nitroglycerin did not result in further plasma cGMP increase compared to sacubitril/valsartan alone. The co-administration of nitroglycerin and sacubitril/valsartan was safe and well tolerated and did not impact the pharmacokinetics of sacubitril/valsartan.Conclusions: The results from this study demonstrate no pharmacodynamic drug interaction between nitroglycerin and sacubitril/valsartan in healthy subjects, suggesting that no change of dose selection and escalation recommendations or clinical monitoring during nitroglycerin administration is required. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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