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10.1111/bcp.12861 http://scihub22266oqcxt.onion/10.1111/bcp.12861 C4834603!4834603 !26663387     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26663387 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Br+J+Clin+Pharmacol 2016 ; 81 (5 ): 878-90 Nephropedia Template TP {{tp|p=26663387 |t=2016. The effect of LCZ696 (sacubitril/valsartan) on amyloid-? concentrations in cerebrospinal fluid in healthy subjects |pdf=|usr=}}{{26663387 }} gab.com Text The effect of LCZ696 (sacubitril/valsartan) on amyloid- concentrations in cerebrospinal fluid in healthy subjects JO: Br J Clin Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26663387 #FOAvip AIMS: LCZ696 (angiotensin receptor neprilysin inhibitor) is a novel drug developed for the treatment of heart failure with reduced ejection fraction. Neprilysin is one of multiple enzymes degrading amyloid-? (A?). Its inhibition may increase A? levels. The potential exists that treatment of LCZ696, through the inhibition of neprilysin by LBQ657 (an LCZ696 metabolite), may result in accumulation of A?. The aim of this study was to assess the blood-brain-barrier penetration of LBQ657 and the potential effects of LCZ696 on cerebrospinal fluid (CSF) concentrations of A? isoforms in healthy human volunteers. METHODS: In a double-blind, randomized, parallel group, placebo-controlled study, healthy subjects received once daily LCZ696 (400 mg, n = 21) or placebo (n = 22) for 14 days. RESULTS: LCZ696 had no significant effect on CSF AUEC(0,36 h) of the aggregable A? species 1-42 or 1-40 compared with placebo (estimated treatment ratios 0.98 [95% CI 0.73, 1.34; P = 0.919] and 1.05 [95% CI 0.82, 1.34; P = 0.702], respectively). A 42% increase in CSF AUEC(0,36 h) of soluble A? 1-38 was observed (estimated treatment ratio 1.42 [95% CI 1.05, 1.91; P = 0.023]). CSF levels of LBQ657 and CSF A? 1-42, 1-40, and 1-38 concentrations were not related (r(2) values 0.022, 0.010, and 0.008, respectively). CONCLUSIONS: LCZ696 did not cause changes in CSF levels of aggregable A? isoforms (1-42 and 1-40) compared with placebo, despite achieving CSF concentrations of LBQ657 sufficient to inhibit neprilysin. The clinical relevance of the increase in soluble CSF A? 1-38 is currently unknown. Twit Text FOAVip The effect of LCZ696 (sacubitril/valsartan) on amyloid- concentrations in cerebrospinal fluid in healthy subjects ????Br J Clin Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26663387 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26663387 #FOAvip English Wikipedia <ref>{{Cite pmid|26663387 }}</ref> The effect of LCZ696 (sacubitril/valsartan) on amyloid-? concentrations in cerebrospinal fluid in healthy subjects #MMPMID26663387 Langenickel TH ; Tsubouchi C ; Ayalasomayajula S ; Pal P ; Valentin MA ; Hinder M ; Jhee S ; Gevorkyan H ; Rajman I Br J Clin Pharmacol 2016[May]; 81 (5 ): 878-90 PMID26663387 show ga AIMS: LCZ696 (angiotensin receptor neprilysin inhibitor) is a novel drug developed for the treatment of heart failure with reduced ejection fraction. Neprilysin is one of multiple enzymes degrading amyloid-? (A?). Its inhibition may increase A? levels. The potential exists that treatment of LCZ696, through the inhibition of neprilysin by LBQ657 (an LCZ696 metabolite), may result in accumulation of A?. The aim of this study was to assess the blood-brain-barrier penetration of LBQ657 and the potential effects of LCZ696 on cerebrospinal fluid (CSF) concentrations of A? isoforms in healthy human volunteers. METHODS: In a double-blind, randomized, parallel group, placebo-controlled study, healthy subjects received once daily LCZ696 (400 mg, n = 21) or placebo (n = 22) for 14 days. RESULTS: LCZ696 had no significant effect on CSF AUEC(0,36 h) of the aggregable A? species 1-42 or 1-40 compared with placebo (estimated treatment ratios 0.98 [95% CI 0.73, 1.34; P = 0.919] and 1.05 [95% CI 0.82, 1.34; P = 0.702], respectively). A 42% increase in CSF AUEC(0,36 h) of soluble A? 1-38 was observed (estimated treatment ratio 1.42 [95% CI 1.05, 1.91; P = 0.023]). CSF levels of LBQ657 and CSF A? 1-42, 1-40, and 1-38 concentrations were not related (r(2) values 0.022, 0.010, and 0.008, respectively). CONCLUSIONS: LCZ696 did not cause changes in CSF levels of aggregable A? isoforms (1-42 and 1-40) compared with placebo, despite achieving CSF concentrations of LBQ657 sufficient to inhibit neprilysin. The clinical relevance of the increase in soluble CSF A? 1-38 is currently unknown. |Adolescent [MESH] |Adult [MESH] |Aminobutyrates/pharmacokinetics/*pharmacology [MESH] |Amyloid beta-Peptides/*cerebrospinal fluid/metabolism [MESH] |Angiotensin Receptor Antagonists/pharmacokinetics/*pharmacology [MESH] |Biphenyl Compounds/pharmacokinetics/*pharmacology [MESH] |Blood-Brain Barrier/*metabolism [MESH] |Double-Blind Method [MESH] |Drug Combinations [MESH] |Female [MESH] |Healthy Volunteers [MESH] |Heart Failure/drug therapy [MESH] |Humans [MESH] |Male [MESH] |Middle Aged [MESH] |Neprilysin/*antagonists & inhibitors [MESH] |Stroke Volume/drug effects [MESH] |Tetrazoles/pharmacokinetics/*pharmacology [MESH] |Valsartan [MESH]The effect of LCZ696 (sacubitril/valsartan) on amyloid-? concentration(epmc).pdf DeepDyve Pubget Overpricing