Shipping to United States We Offer Worldwide Shipping
Login Wishlist

2′,4′,6′-Trihydroxyacetophenone

$43

  • Brand : BIOFRON

  • Catalogue Number : AV-C96090

  • Specification : 98%

  • CAS number : 480-66-0

  • Formula : C8H8O4

  • Molecular Weight : 168.2

  • PUBCHEM ID : 68073

  • Volume : 20mg

Available on backorder

Quantity
Checkout Bulk Order?

Catalogue Number

AV-C96090

Analysis Method

HPLC,NMR,MS

Specification

98%

Storage

2-8°C

Molecular Weight

168.2

Appearance

Botanical Source

Structure Type

Category

Standards;Natural Pytochemical;API

SMILES

CC(=O)C1=C(C=C(C=C1O)O)O

Synonyms

1-(2,4,6-Trihydroxyphenyl)-ethanone/2-Acetylphloroglucinol/Ethanone, 1- (2,4,6-trihydroxyphenyl)-/2-Acetylphloroglucinol Monohydrate/Phloroacetophenone/Ethanone, 1-(2,4,6-trihydroxyphenyl)-/2',4',6'-Trihydroxyacetophenone Monohydrate/2-Acetylphloroglucinol,THAP/2',4',6'-Trihydroxyaceto-phenone/2,4,6-trihydroxyacetophenone/Phloroacetophenone Monohydrate/1-(2,4,6-Trihydroxyphenyl)ethanone/Phloracetophenone

IUPAC Name

1-(2,4,6-trihydroxyphenyl)ethanone

Applications

Phloracetophenone (2,4,6-trihydroxyacetophenone) is the aglycone part of acetophenone glycoside obtained from Curcuma comosa Roxb, with cholesterol-lowering activity. Phloracetophenone enhances cholesterol 7α-hydroxylase (CYP7A1) activity[1]. Phloracetophenone stimulats bile secretion mediated through Mrp2[2].

Density

1.4±0.1 g/cm3

Solubility

Flash Point

169.5±18.8 °C

Boiling Point

333.2±22.0 °C at 760 mmHg

Melting Point

219-221 °C(lit.)

InChl

InChl Key

WGK Germany

RID/ADR

HS Code Reference

2914500000

Personal Projective Equipment

Correct Usage

For Reference Standard and R&D, Not for Human Use Directly.

Meta Tag

provides coniferyl ferulate(CAS#:480-66-0) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate

No Technical Documents Available For This Product.

PMID

30023859

Abstract

The present work highlights the effect of urea on solvation dynamics and the rotational relaxation of Coumarin 480 (C-480) in the Stern layer of aqueous micelles of cationic gemini surfactants, 12-4(OH)n-12 (n = 0, 1, 2). UV-visible absorption, steady-state fluorescence and fluorescence anisotropy, time-resolved fluorescence and fluorescence anisotropy, and dynamic light scattering measurements have been carried out for this study. The formation of micelles becomes disfavored in the presence of urea at high concentration. Solvation dynamics is bimodal in nature with fast solvation as a major component. The average solvation time increases, reaches a maximum, and then decreases with increasing concentration of urea because the degree of counterion dissociation also follows the same order with the addition of urea in the micellar solution. With increased degree of counterion dissociation, the extent of clustering of water molecules is increased, resulting in slower solvation process. The ?OH group present in the spacer group of gemini surfactant controls the rate of solvation by shielding the water molecules from the probe molecules forming hydrogen bond. The microviscosity of micelles is decreased with increasing concentration of urea, as a result of which the rotational relaxation process becomes faster. In the presence of the ?OH group in the spacer group, the microviscosity of micelles is enhanced, resulting in longer rotational relaxation time. Rotational relaxation process is bimodal in nature with the major contribution from the fast component to the fluorescence depolarization. Slow rotational relaxation is mainly due to the lateral diffusion of C-480 molecules along the surface of the micelle. The tumbling motion of the micelle as a whole is much slower than the lateral diffusion of C-480. Wobbling motion of C-480 becomes faster with increasing concentration of urea as a result of decreased microviscosity of micelles. The alignment of C-480 molecules in micelles might change with changing microviscosity.

Title

Effect of Urea on Solvation Dynamics and Rotational Relaxation of Coumarin 480 in Aqueous Micelles of Cationic Gemini Surfactants with Different Spacer Groups

Author

Sunita Kumari,† Sonu,†§ Sayantan Halder,† Rishika Aggrawal,† Ganapathisubramanian Sundar,corresponding author*‡ and Subit K. Sahacorresponding author*†

Publish date

2018 Mar 31;

PMID

27316915

Title

French Intensive Care Society, International congress - Reanimation 2016

Author

Emmanuelle Jaillette,corresponding author1 Christophe Girault,2 Guillaume Brunin,3 Farid Zerimech,4 Arnaud Chiche,5 Celine Broucqsault-Dedrie,6,7 Cyril Fayolle,8 Franck Minacori,9 Isabelle Alves,10 Stephanie Barrailler,11,12 Laurent Robriquet,1 Emmanuel Delaporte,3 Damien Thellier,5 Claire Delcourte,1 Alain Duhamel,13,14 Saad Nseir,1 Xavier Valette,corresponding author15 Isabelle Desmeulles,16 Benoit Savary,17 Romain Masson,16 Amelie Seguin,15 Cedric Daubin,15 Bertrand Sauneuf,corresponding author15,18 Pierre Verrier,15 Veronique Pottier,16 Marie Orabona,16 Desire Samba,16 Gerald Viquesnel,16 Mathilde Lermuzeaux,16 Pascal Hazera,17 Jean-Luc Hanouz,16,19 Jean-Jacques Parienti,20 Damien Du Cheyron,15 Alexandre Demoule,corresponding author21,22,23 Marc Clavel,24 Camille Rolland-Debord,21 Sebastien Perbet,25 Nicolas Terzi,15,26 Achille Kouatchet,27,28 Florent Wallet,29,30 Hadrien Roze,31,32 Frederic Vargas,33 Claude Guerin,34 Jean Dellamonica,35 Samir Jaber,36 Thomas Similowski,21,22 Jean-Pierre Quenot,corresponding author37 Christine Binquet,38 Christophe Vinsonneau,39,40 Saber-Davide Barbar,41 Sandrine Vinault,38 Valerie Deckert,42 Stephanie Lemaire,42 Ali Ait Hssain,43 Remi Bruyere,37,44,45 Bertrand Souweine,43 Laurent Lagrost,42 Christophe Adrie,46,47,48,49 Boris Jung,corresponding author36 Aurelien Daurat,36 Audrey De Jong,corresponding author36 Gerald Chanques,36 Martin Mahul,36 Marion Monnin,36 Nicolas Molinari,50 Olivier Lheureux,corresponding author51 Eric Trepo,52 Maya Hites,53 Frederic Cotton,54 Fleur Wolff,54 Rudy Surin,53 Jacques Creteur,51 Jean-Louis Vincent,51,55 Thierry Gustot,52 Frederique Jacobs,53 Fabio Silvio Taccone,corresponding author51 Mathilde Neuville,corresponding author56,57,58,59 Jean-Francois Timsit,57,60,61 Najoua El-Helali,62 Alban Le Monnier,62 Eric Magalhaes,56,57 Aguila Radjou,56,57 Roland Smonig,56,57,63 Jean-Francois Soubirou,56,57 Guillaume Voiriot,56,57 Romain Sonneville,56,57,64 Lila Bouadma,56,57,65 Bruno Mourvillier,56,57,66 Elodie Gelisse,corresponding author67 Alexandre Brasseur,corresponding author68 Sandrine Roisin,69 Daniel De Backer,70 Valerie Van Ruychevelt,corresponding author71 Eric Carlier,71 Michael Piagnerelli,71,72,73 Michel Vanhaeverbeek,74 Christine Danguy,75 Patrick Biston,71,72,73,76 Siu-Ming Au,77 Emmanuelle Begot,24,78,79 Francois Dalmay,80,81 Xavier Repesse,82 Gwenael Prat,83 Koceila Bouferrache,84 Michel Slama,85 Antoine Vieillard-Baron,corresponding author82 Xavier Monnet,corresponding author86 Paul Marik,87 Jean-Louis Teboul,86,88,89 Mathieu Jozwiak,corresponding author88,90 Christian Richard,88,90 Jean-Louis Chauvet,corresponding author91 Shari El-Dash,85,92 Olivier Delastre,91 Bernard Bouffandeau,91 Dominique Jusserand,91 Jean-Baptiste Michot,91 Fabrice Bauer,93 Francois Brazier,85 Pablo Mercado,85 Loay Kontar,85 Dimitri Titeca,85 Bertand De Cagny,85 Gaelle Bacari-Risal,85,94 Antoine Riviere,85 Julien Maizel,corresponding author85 Camille Guillot,95 Claire Le Reun,95,96 Marie Lampin,95 Ahmed Sadik,95 Astrid Botte,95,96 Stephane Leteurtre,corresponding author95 Aurelie Collins,corresponding author97 Celine Kempeneers,98 Nathalie Cajgfinger,99 Camille Ohlmann,100 Robin Pouyau,corresponding author100,101 Fabien Subtil,102,103 Florent Baudin,100 Bruno Massenavette,100 Etienne Javouhey,100 Christophe Milesi,corresponding author104 Sandrine Essouri,105 Jean-Michel Liet,106 Mickael Afanetti,107,108 Sabine Durand,104 Philippe Durand,105 Jean Christophe Roze,106 Didier Dupont,107 Gilles Cambonie,104,109 Benjamin Soyer,corresponding author110 Marco Rusca,110 Anne-Claire Lukaszewicz,110,111 Isabelle Crassard,112 Jean-Pierre Guichard,113 Damien Bresson,114 Didier Payen de la Garanderie,110,111 Marie Cantier,corresponding author64 Candice Sabben,64 Liliane Louedec,64 Sandrine Delbosc,64 Clement Journe,64 Phalla Ou,64 Isabelle Klein,64 Francoise Chau,115 Agnes Lefort,116 Jean-Philippe Desilles,64 Jean-Baptiste Michel,64 Mika?l Mazighi,64 Omar Ben Hadj Salem,corresponding author117 Sophie Demeret,118,119 Francis Bolgert,120 Tarek Sharshar,121 David Grabli,122 Safa Arib,123 Ilaria Alice Crippa,123 Alexis Soummer,corresponding author124 Nicolas Engrand,125 Pierre Guedin,126 Sorin Aldea,127 Charles Cerf,124,128 Victoire Desailly,129 Pierre Pasquier,130 Patrick Brun,131 Damien Roux,129,132 Gwendoline Latournerie,129 Laetitia Kasprzyk,129 Vincent Grosjean,129 Amine Latreche,129 Pierre Habert,129 Stephane Huot,129 Timon Jobin,129 Antoine Tesniere,133 Didier Dreyfuss,129,134 Jean-Damien Ricard,129,132,135 Alexandre Mignon,133 Stephane Gaudry,corresponding author129 Francois-Xavier Laithier,136 Antoine Kimmoun,corresponding author136 Tahar Chouihed,137 Stephane Albizzati,137 Edoardo Camenzind,138 Fabrice Vanhuyse,139 Bruno Levy,136 Martin Cour,140 Fabienne Venet,141 Romain Hernu,140 Julie Demaret,141,142 Guillaume Monneret,141 Laurent Argaud,corresponding author140 Florence Dumas,corresponding author143,144 Lionel Lamhaut,145 Julien Rosencher,146 Frederic Pene,147 Olivier Varenne,148 Pierre Carli,149 Xavier Jouven,150 Christian Spaulding,150 Alain Cariou,147 Guillaume Geri,corresponding author147 Franck Bonnetain,151 Eloi Marijon,152 Jean Philippe Empana,153 Adrien Mirouse,corresponding author154 Matthieu Resche-Rigon,155,156 Julien Mayaux,21,23,157,158 Antoine Rabbat,159,160 Anne Pascale Meert,161 Dominique Benoit,162 Fabrice Bruneel,163 Elie Azoulay,164,165 Claire Dupuis,corresponding author166,167 Carole Schwebel,165,168 Stephane Ruckly,169 Dany Goldgran-Toledano,170 Guillaume Marcotte,171,172 Antoine Lafarge,corresponding author173 Claire Pichereau,173,174 Igor Theodose,173 Marion Scotto,173 Delphine Kemlin,173 Etienne Ghrenassia,173 Beno?t Schlemmer,173 Damien Vimpere,corresponding author173 Lionel Galicier,175 Damien Contou,corresponding author176 Emmanuel Guerot,177 David Grimaldi,178,179 Sylvie Ricome,180 Eric Maury,181,182 Ga?tan Plantefeve,183 Armand Mekontso Dessap,184 Christian Brun-Buisson,184 Nicolas de Prost,184,185 Bruno-Pierre Dube,21 Julie Delemazure,21 Martin Dres,corresponding author21,23 Ludivine Rousseau,corresponding author186 Xavier Drouot,187 Veronique Diaz,187 Yohann Rebollar,187 Jean-Pierre Frat,186 Arnaud W. Thille,186 Groupe ALIVE, Dalinda Ait Aissa,188 Pierre Coquet,189 Jean Ruiz,190 Fabrice Ferre,188 Lucille Hoarau,188 Beatrice Riu-Poulenc,188 Benoit Bataille,189 Stein Silva,corresponding author191,192 Jean-Luc Baudel,182 Na?ke Bige,193,194,195 Jalel Tahiri,182,193 Vincent Dubee,182,193 Bertrand Guidet,182,193 Hafid Ait-Oufella,corresponding author182,193 Liu Jinglun,86 Feng Shen,86 Xavier Monnet,corresponding author86,88 Sebastien Bailly,corresponding author196,197 Olivier Leroy,5 Philippe Montravers,198 Jean-Michel Constantin,199 Herve Dupont,200 Didier Guillemot,201 Olivier Lortholary,202 Pierre-Francois Perrigault,203 Jean-Pierre Gangneux,204 Keyvan Razazi,corresponding author205 Armand Mekontso-Dessap,184 Chloe Jansen,206 Marie Lecronier,corresponding author23 Valade Sandrine,164,207 Jean-Paul Mira,corresponding author147,208 Sophie Blein,209 Nathalie Marin,147 Christophe Rousseau,210 Julien Charpentier,147 Alexandre Pachot,211 Sami Hraiech,corresponding author212,213 Julien Bordes,214 Lamballerie Xavier De,215 Jean-Louis Mege,216 Jean-Marie Forel,217 Christophe Guervilly,217 Melanie Adda,217 Didier Raoult,216 Laurent Papazian,213,218 Nancy Kentish-Barnes,corresponding author219 Zoe Cohen-Solal,219 Nancy Kentish-Barnes,corresponding author219 Virginie Souppart,173 Lionel Kerhuel,corresponding author192 Carole Haubertin,192 Isabelle Exbrayat,192 Elodie Rozieres,192 Audrey Argain,192 Agnes Suc,220 Michel Vignes,221 Pierre Cougot,222 Olivier Fourcade,192,223 Elodie Brunel,192 Jonathan Messika,corresponding author129 Florence Tubach,224 Emeline Dubief,129 Blandine Pasquet,224 Sylvie Guillo,224 Charlotte Pierron,corresponding author225,226 Marion Grimaud,227 Caroline Farnoux,228 Amelie Maillard,229 Maxens Decavele,corresponding author230 Helene Prodanovic,22 Ahmed Idbaih,231 Agusti Alentorn,231 Jean-Yves Delattre,231 Etienne De Montmollin,corresponding author232 Noelle Brule,233 Marie Conrad,234 Frederic Dailler,235 Jean-Christophe Navellou,236 Mikael Alves,193,237,238 Jean-Marie Tonnelier,239 Stephane Ruckly,56,240,241,242,243 Geraldine Picard,244 Veronique Rogemond,244 Jer?me Honnorat,244 ENCEPHALITICA Study Group, Chiara Marzorati,245 Christine Lebert,246 Pierre Perez,247 Giuseppe Citerio,245 Stephane Legriel,corresponding author163,248 Simona Tripon,corresponding author249,250 Maxime Mallet,249,251 Marika Rudler,249,250 Francoise Imbert-Bismut,252 Dominique Thabut,249,250 Emmanuel Canet,corresponding author173,253 Stanislas Faguer,254 Anne-Sophie Moreau,255 Francois Barbier,256 Sybille Merceron,163 Christophe Guitton,257,258 Francois Labadie,259 Virginie Lemiale,corresponding author173,260 Etienne Faucher,140 Kada Klouche,261,262,263 Sylvie Chevret,264 Groupe de Recherche en Reanimation Respiratoire du patient d’Onc-hematologie, Stephanie Ragot,265 Remi Coudroy,corresponding author186 Thierry Boulain,266 Angeline Jamet,186 Alain Mercat,28 Laurent Brochard,267 Antoine Roux,128,268 Virginie Lemiale,corresponding author260 Guillaume Franchineau,corresponding author269 Nicolas Brechot,270,271 Guillaume Lebreton,272,273,274 Guillaume Hekimian,270,275,276 Ania Nieszkowska,271,277 Pascal Leprince,273,274,278,279,280 Jean Louis Trouillet,271,281 Alain Combes,271,282,283 Matthieu Schmidt,22,271,276,284 Lo?c Barrot,corresponding author236 Ga?l Piton,285 Michael Bailey,286 Rakshit Panwar,286 Nicolas Belin,236 Francois Belon,236 Cyrille Patry,236 Mathilde Grandperrin,236 Claire Chaignat,236 Guylaine Labro,285 Berengere Vivet,236 Gilles Capellier,236 Thomas Daix,corresponding author287 Estelle Guerin,288,289 Elsa Tavernier,290 Emmanuelle Mercier,291,292 Valerie Gissot,293 Christine Vallejo,294 Bruno Francois,24,295,296,297 Septiflux trial Group, Celine Ravry,298 Nicolas Pichon,24,78,79 Catherine Chapellas,24,299 Anne-Laure Fedou,24,79,300 Antoine Galy,24,299 Marie-Cecile Ploy,301 Olivier Barraud,301 Philippe Vignon,corresponding author24,298 Aurelie Thooft,corresponding author302 Raphael Conotte,303 Jean-Marie Colet,303 Matthieu Le Dorze,corresponding author111 Virginie Tarazona,111 Caren Brumpt,304 Helene Moins-Teisserenc,305 Fabrice Uhel,corresponding author63,306 Imane Azzaoui,307 Murielle Gregoire,308 Celine Pangault,309 Jo?lle Dulong,309 Luc Cynober,310 Mika?l Roussel,309 Yves Le Tulzo,63,306 Karin Tarte,308 Julien Demiselle,311 Johann Auchabie,312 Pierre Francois Dequin,313 Nicolas Chudeau,314 Francois Fourrier,315 Steven Grange,2 Lise Piquilloud,316 Alexandre Lautrette,43 Sonia Boyer,317 Julien Letheulle,318,306 Nicolas Lerolle,corresponding author27 Anne Sophie Truche,corresponding author167,168,319 Christophe Clec’h,320 Philippe Zaoui,321 Virginie Laurent,322 Dany Goldgran Toledano,323,324 Sophie Perinel Ragey,325 Antoine Gros,163 Anne Sylvie Dumenil,326,327 Samir Jamali,328 Micha?l Darmon,corresponding author329 For the OUTCOMEREA Study Group, Mikhael Chouraqui,330 Antoine Dewitte,corresponding author330,331 Brigitte Chastel,330 Pauline Carles,330 Catherine Fleureau,330,331 Olivier Joannes-Boyau,330,331 Alexandre Ouattara,32,330,331,332,333 Adrien Joseph,corresponding author173,334 Ma?te Garrouste-Orgeas,corresponding author335 Adeline Max,336 Talia Lerin,337 Charles Gregoire,336 Martin Kloeckner,336 Cedric Bruel,338 Sandie Brochon,339 Francois Philippart,336,340 Emmanuelle Pichot,336 Clara Simons,338 Andrew Flint,286 Cecile Aubron,corresponding author341,342 Rinaldo Bellomo,286 David Pilcher,343 Allen Cheng,344 Colin Hegarty,345 Anthony Martinelli,345 Benjamin Howden,346 Michael Reade,346,347 Zoe Mcquilten,348 Cedric Bretonniere,corresponding author349 Daniel Villers,349 Groupe RMM, Qualite et Securite des Soins - CBPR-CFAR, M. Soares,350 Frederic Gonzalez,351,352 Francois Vincent,corresponding author353,354 For the GrrrOH: Groupe de recherche en reanimation respiratoire en Onco-Hematologie (Group for Research in Respiratory Intensive Care Onco-Hematology, Clemence Fauche,355 Samuel Gay,corresponding author355,356 Olivier Skowron,357,358 Albrice Levrat,355,356 Didier Dorez,359,360 Maxens Decavele,corresponding author230 Arnaud Foucrier,361 Sebastian Pease,361 Tobias Gauss,361 Catherine Paugam,361,362 Julie Gorham,corresponding author363 Lieveke Ameye,364 Marianne Paesmans,364 Thierry Berghmans,363 Jean-Paul Sculier,363 Anne-Pascale Meert,363 Pauline Deras,365 Orianne Martinez,365 Pascal Latry,366 Xavier Capdevila,365 Jonathan Charbit,365 J. Jaubert,367 Celia Etiennar,368 Lucie Ginoux,368 Jean-Luc Sebbah,368 Hakim Haouache,367 Gilles Dhonneur,corresponding author367,369 Chaigar Mohammed Cheikh,corresponding author370 I. Moussaid,370 O. Ghazaoui,370 Kamal Belkadi,370 S. El Youssoufi,370 S. Salmi,370 Laure Pajot,371 Benjamin Zuber,corresponding author371,372 Michael Darmon,166 Jean Pierre Bedos,371 OutcomeRea, Benoit Dupont,373 Axelle Eugene,374 Francoise Galateau-Salle,374 Baptiste Michard,375 Benjamin Lebas,corresponding author375 Alexandra Boivin,375,376,377 Max Guillot,86,375,377,378 Marie-Line Harlay,375,377 Ralf Janssen-Langenstein,375,377,378 Maleka Schenck,375,376,377,378 Bernard Ellero,379 Marie-Lorraine Woehl-Jaegle,379 Camille Besch,379 Vincent Castelain,375,378,377,380 Philippe Bachellier,379 Francis Schneider,375,376,377,378 Christophe Camus,corresponding author381 Fawzi Saliba,382 Bernard Goubaux,383 Agnes Bonadona,384 Laurence Lavayssiere,385 Alice Quinart,386 Olivier Barbot,387 Sebastien Dharancy,388 Bertrand Delafosse,389 Helene Barraud,390 Arnaud Galbois,193,391 Benoit Veber,392 Sophie Cayot,393 Bruno Souche,394 Clara Locher,395 RETROMARS Study Group, Olivier Roux,corresponding author396 Francesco Figorilli,397 Antonella Putignano,397 Pauline Houssel,398 Claire Francoz,398 Emmanuel Weiss,399 Banwari Agarwal,400 Rajiv Jalan,397 Francois Durand,401 Hassen Ben Ghezala,corresponding author402 Rebeh Daoudi,402 Moez Kaddour,402 Hatem Ghadhoune,corresponding author403 E. Rachedi,403 J. Guissouma,403 A. Ben Slimene,403 W. Azzeza,403 H. Brahmi,403 H. Elghord,403 Ahmed Youssef Kada,corresponding author404 Radia Chikh,404 Roza Slimani,404 Kheireddine. a Bouyoucef,404 Kais Regaieg,405,406 Chtara Kamilia,corresponding author405 Najeh Baccouche,406,407 Olfa Turki,405,407 Anis Chaari,405 Hmida Chokri Ben,405 Mounir Bouaziz,406 Fatma Kaaniche Medhioub,corresponding author408 Manel Zekri,407 Kais Rgieg,407 Chokri Bhimada,405 Bouaziz Mounir,405 Chaigar Mohammed Cheikh,corresponding author370 Elodie Lang,409 Stephane Welschbillig,corresponding author409,410 Mathilde Perrin,corresponding author411 Jean-Michel Devys,411 Soumia Benbernou,corresponding author412 Houria Mokhtari-Djebli,412,413 Sofiane Ilies,412 Khalida Bouyacoub,414 Abdelkader Azza,414 Elie Zogheib,corresponding author415 Joseph Nader,416 Leonie Villeret,415 Mathieu Guilbart,415 Patricia Besserve,415 Thierry Caus,416 Ciro Mastroianni,273 Francesca Santi,273 Guillaume Hekimian,271,276,417 Leprince Pascal,273 Jean Chastre,271,276,283 Virginie Perrier,32,332 Benjamin Deniau,129 Fanny Klasen,213,218,418 Jean Pierre Ponthus,419 Polysie Ngasseu,419 Virginie Amilien,419 Elise Barsam,419 Pierre Lehericey,419 Martial Tchir,419 Jean Francois Georger,419 Berenice Puech,420 David Vandroux,420 Arnaud Roussiaux,420 Dominique Belcour,420 Cyril Ferdynus,421 Olivier Martinet,420 Julien Jabot,420 Marion Fresco,392 Ga?lle Demeilliers-Pfister,392,422 Veronique Merle,423 Valery Brunel,424 Bertrand Dureuil,425 Sebastien Leydier,234 Isabelle Clerc-Urmes,426 Jeremie Lemarie,234 Charles-Henri Maigrat,234 Aurelie Cravoisy-Popovic,234 Damien Barraud,234 Lionel Nace,234 Sebastien Gibot,234 Nelly Agrinier,426 Pierre-Edouard Bollaert,234 Jean-Louis Daban,427 Mathieu Boutonnet,427 Guillaume Dumas,427 Elisabeth Falzone,427 Patrick Jault,428 Bernard Lenoir,428 Joseph Nsiala Makunza,429 Nathalie Mejeni,430 Amelie Mazaud,431 Sebastien Beague,432 Anne-Flore Rousselle,433 Alain Durocher,434 For the BIBLIOFLASH Study Group, Pauline Perez,435 Alexandra Grinea,435 Naoures Bedoui,402 Alina Stoian,34 Loredana Baboi,34 Florent Gobert,34 Hodane Yonis,34 Romain Tapponier,34 Arnaud Bruyneel,436 Thierry Bonus,437 Gregory Cuvelier,438 Sharam Machayeckhi,437 Sandra Olieuz,437 Alexandre Legrand,439 Fatma Feki,440 Amira Jamoussi,440 Takoua Merhebene,440 Emna Braham,441 Asma Ghariani,442,443 Faouzi El Mezni,441 Leila Slim,442 Jalila Ben Khelil,440,444 Mohamed Besbes,440,444 Antoine Marchalot,445 Gaetan Beduneau,2 Dorothee Carpentier,2 Emmanuel Besnier,2,446 Gioia Gastaldi,2 Julien Abily,2 Marion Beuzelin,2 Mai-Anh Nay,266 Julie Mankikian,313 Virginie Herve,447 Marie Soulie,448 Pierrick Cronier,448 Elie Kantor,448 Laura Federici,448 Marion Gilbert,448 Ilham Mezhari,448 Gerald Choukroun,448 Sophie Marque,448 Z. Coppere,230 Jean-Pierre Fulgencio,230 Clarisse Blayau,230 Tai Pham,230 Michel Djibre,230 Matthieu Reffienna,147 Sebastien Lefort,147 Anne-Sophie Debue,147 Fabrice Daviaud,147 Sarah Cabon,147 Working Group on Mechanical Ventilation, Zakaria Addou,449 Ali Douah,450 Mohamed Moussati,450 Kamel Belhabiche,450 Nabil Aouffen,450 Sylvie Soulier,333 Philippe Mauriat,451 Nadir Tafer,451 Guillaume Mortamet,452 Alessandro Amaddeo,453 Sonia Khirani,453 Brigitte Fauroux,453 Gennadiy Khanes,454 Olga Liutko,455 Svitlana Bidnenko,455 Emilie Doye,456 Nicolas Voirin,457 Delphine Maucort-Boulch,457 Karine Kolev-Descamp,101 Imane El Aouane,458 Aben Essid,458 Wallid Hammami,459 Isabelle Haegy,458 Jacques Bataille,459 Jean Bergounioux,460 Luc Morin,461 Samiran Ray,462 Graeme Maclaren,463 Simon Nadel,464 Martin Kneyber,465 Mark Peters,462 Koos Jansen,466 Daniele De Luca,467 Clare Wilson,464 Luregn Schlapbach,468 Pierre Tissieres,461 Anne-Claire Girard,469 Elodie Savajols,470 Antoine Burguet,470 Denis Semama,470 Stephanie Litzler-Renault,471 Hana Fredj,472,473 Malek Hassouna,472 Youssef Zied El Hechmi,472 Mohamed Ali Cherif,472 Jerbi Zouheir,472 Ahmed Dernane,474 Fouad Bouakkaz,412 Lhoucine Ben Taleb,475 A. Zeddine Mouhsen,475 Aissam Lyazidi,476 Jean-Christophe Marie Richard,477 Ahmed Mouhsen,478 Mohammed Harmouchi,475 Mourad Rattal,476 Matthias Huck,479 Thomas Leclerc,479 Nicolas Donat,479 Audrey Cirodde,479 Jean-Vivien Schaal,479 Yannick Masson,479 Clement Hoffmann,479 Laura Cerland,480 Ruddy Valentino,480 C. Chabartier,480 Laurent Villain-Coquet,481 Jean-Louis Ferge,480 Y. Brouste,481 Hossein Mehdaoui,480 Maha Louriz,482 Naoufal Madani,482 Fatiha Amlaiky,482 Tarek Dendane,483 Khalid Abidi,483 Aicha Zekraoui,482 Amine Ali Zeggwagh,483 Redouane Abouqal,482 Affra Brahim,484 Fehmi Ferhi,484 Mohamed Amine Bouslama,484 Khaled Benjazia,484 Abid Zeineb,485 Dhaouadi Mahassen,486 Julien Cadiet,487 Marine Ferron,488 Valentine Prat,488 Angelique Erraud,488 Virginie Aillerie,488 Mathieu Mevel,489 Amandine Grabherr,488 John C. Chatham,490 Chantal Gauthier,488 Benjamin Lauzier,488 Bertrand Rozec,491 Jeremie Joffre,182 Xavier Loyer,492 Jean-Remi Lavillegrand,182,193 Lynda Zeboudj,492 Ludivine Laurans,492 Bruno Esposito,492 Alain Tedgui,492 Ziad Mallat,492 Chaojie Wei,493 Narimane Al Kattani,493 Huguette Louis,494 Sophie Orlowski,495 Pierre-Louis Tharaux,492 Melanie Burban,496 Gregory Meyer,497 Anne Olland,498 Blandine Yver,499 Florence Toti,496 Valerie Schini-Kerth,496 Alexandra Monnier,500 Pierrick Leborgne,501 Ferhat Meziani,500 Thomas Clavier,446 Mulder Paulus,502 Helene Castel,503 Vincent Richard,502,504 Stephanie Pons,505 David Skurnik,505 Sophie Six,1 Karim Jaffal,1 Clara Vigneron,37 Audrey Large,37,506 Julien Bador,506,507 Serge Aho,508 Sebastien Prin,37,506 Yosr Touil,509 Soufia Ayed,509 Habiba Sik Ali,509 Najla Tilouch,509 Houda Mateur,509 I. Talik,509 Rim Gharbi,509 Mohamed Fekih Hassen,509 Souheil Elatrous,509 Isabelle Patry,510 Xavier Bertrand,511 Jean-Ralph Zahar,512 Wafa Essaied,513 Martin Wolkewitz,514 Micka?l Soued,369 Fabrice Cook,369 David Lobo,369 Roman Mounier,369,515 Aurelie Emirian,516 Jean Winoc Decousser,516 Mohamed Toufik Slaoui,517 Abdellatif Benslama,517 Dorothee Valance,420 Nicolas Allou,420 Jer?me Allyn,420 Elodie Jean-Bart,518 Floriane Bel.,518 Fabienne Morey,518 Nicholas Sedillot,45 Lucie Biard,264 Richard Galliot,420 Romain Zunarelli,420 Bernard-Alex Gauzere,420 Jean-Charles Cartier,519 Thomas Jouve,520 Marie-No?lle Hilleret,521 Rebecca Hamidfar-Roy,522 Claire Ara-Somohano,519 Clemence Minet,168 Aline Pourcelet,523 Jean-Michel Hougardy,523 Pierre Defrance,76 Louis De Laforcade,524 Alexandre Boyer,525 Didier Gruson,525 Benjamin Clouzeau,525 Najah Hajjam,472 Houda Nasri,472 Hamdi Doghri,472 Nicolas Mongardon,367 Eric Levesque,367 Marie-Ana?s Bastide,85 Jack Richecoeur,526 Eric Frenoy,527 Christian Lemaire,528 BoReal study group, Frederique Schortgen,184 Sebastien Preau,434 Franck Ehooman,351 Claire Montlahuc,156 Jean Bardon,529 Nicolas Postel-Vinay,530 Mehdi Lafi,327 Frederic Jacobs,327 Dominique Prat,327 Matthieu Le Meur,327 Guy Moneger,327 Nadege Demars,327 Pierre Trouiller,327 Noemie Tence,327 Ines Zaien,327 Martine Wolf,531 Jer?me Allardet-Servent,532 Melissa Lebsir,533 Christian Dubroca,533 Mireille Portugal,533 Matthias Castanier,532 Thomas Signouret,532 Rettinavelou Soundaravelou,532 Anne Lepidi,532 Philippe Halfon,533 Jean-Marie Seghboyan,532 Camille Gamblin,534 Nadia Benturquia,534 Olivier Roussel,534 Lucie Chevillard,534 Patricia Risede,534 Jacques Callebert,534 Messaouda Khelfa,473 Youssef Blel,473 H. Thabet,535,536 Nozha Brahmi,473 M. Amamou,473,537 A. Lillo- Le Lou?t,538 F. Baud,539 C. Le Beller,538 B. Vivien,539 L. Soufir,540 P. Carli,539 H. Le Lou?t,541 Fatma Essafi,473 Nasreddine Foudhaili,473 Abdelaziz Ben Slimen,473 Rami Jabla,542 Hedia Hammed,542 Mahdi Marzouk,542 Nesrine Boujelbene,542 Fahmi Dachraoui,542 Asma Hachani,542 Saousen Ben Abdallah,542 Hend Ben Lakhal,473,542 Chaima Ghribi,542 Imen Ben Ali,542 Imen Abdellaoui,542 Lamia Ouanes-Besbes,542 Fekri Abroug,542 Suela Demiri,543 Christine Lorut,159 Daniel Luu Van Lang,544 Aurelie Lefebvre,159 Marco Alifano,545 Jean-Francois Reignard,545 Marc Samama,544 Daniel Dusser,159 Nicolas Roche,159 Francois Reminiac,546,547 Cassandre Landel,548 Samuel Gensburger,548 Thomas Bocar,548 Lydiane Mordier,548 Marion Philippe,548 Deborah Le Pennec,548 Laurent Vecellio,548 Stephan Ehrmann,313 Laurent Poiroux,549 David Thevoz,550 Julien Simons,550 Jean Roeseler,551,552 Anthea Loiez,553 Stephanie Gerard,554 Nicolas Dousse,555 Sylvie L’hotellier,377,556 Elodie Baumgarten,557 Stephanie Borschneck,380 Fatima Kharcha,558 Cecile Ghander,558 Christophe Tresallet,559 Etienne Puymirat,560 Jean-Yves Fagon,177 Philippe Aegerter,561 Jean-Luc Diehl,177 Caroline Hauw-Berlemont,177 Gilles Chatellier,562 Nicolas Danchin,150 Nadia Aissaoui,177 Nadia Aissat,563 R. Bernard,563 Julien Amour,564,565 Adrien Bougle,563,565 Charles Vidal,565 Djavidi Nima,565 Varnous Shaida,273 Amandine Dorget,275 Nicolas Brechot,275,276 Rabi Toufiki,566 Youssef Mouaffak,566 Ahmed Rhassan El Adib,566 M. Amine,567 S. Moumine,370 Marie Jonard,568 Anne Sophie Ducloy-Bouthors,569 Pierre Bouju,306 Nicolas Barbarot,570 Arnaud Gacouin,63,306 Pierre Fillatre,306 Guillaume Grillet,306 Angelique Goepp,570 Anne-Laure Clairet,236 Samuel Limat,571 Christian Cornette,571 Amira Fatnassi,572 Chiheb Romdhani,572 Walid Sammoud,572 Iheb Labbene,572 Mustapha Ferjani,572 Hind Taibi,corresponding author573 Ijlal Elatiqi,573 A. Iraqui,574 Rachid Cherkab,573 Wafae Haddad,573 Chafik Elkettani,573 Lahoucine Barrou,573 Fabien Cave,27 Nicolas Lerolle,corresponding author27 Pierre Louis Doutrellot,575 Benoit Vaysse,576 M. Inan,577 K. Khelfoun,578 M. Nasserallah,579 Julien Maizel,corresponding author85 C. Legrand-Monteil,580 S. Tasseel-Ponche,575 Benjamin Kowalski,corresponding author581 Anne Guaguere,582 Claire Boulle-Geronimi,583 Juliette Masse,corresponding author584,585 Clement Vanbaelinghem,7 Patrick Herbecq,7,584 Amel Mokline,corresponding author586 Syrine Draief,586 Lazhari Gharsallah,586 Imen Rahmani,586 Bahija Gasri,586 Sofiene Tlaili,586 Rym Hammouda,586 Amen Allah Messadi,586 Philippe Michel,corresponding author587 Bruno Gelee,526 Fouad Fadel,587 Marie Thuong,587 Sandra Ait-Aoudia,corresponding author588 Salima Laddi,588 Mohamed-Mohcen Sahraoui,588 Michel Muller,corresponding author355,356 Anna Faucher,360 Bertrand Hermann,177 Caroline Hauw Berlemont,corresponding author177 Michel Arnaout,corresponding author147 Julie Busson,147 Julie Dhumeaux,147 Nicole Ericher,147 Pierre Lucas,147 Groupe de travail sur la ventilation, Magalie Dumas,corresponding author589 Celine Chapelle,590 Benedicte Philippon-Jouve,591 Jerome Morel,592 Pascal Beuret,591 C?me Bureau,corresponding author21 Tymothee Poitou,593 Universite Paris 6 ?Pierre et Marie Curie and Institut National pour la Sante et la Recherche Medicale, UMRS1158, Paris, Remi Coudroy,corresponding author186 Philippe Petua,186,594 Hassen Ben Ghezala,corresponding author402 Albert Prades,36 Marion Basty,36 Clement Monet,36 Benjamin Mounet,36 Emmanuel Futier,595 Audrey Leroux,corresponding author596 Xavier Oudinot,596 Marc Laurent,596 Islem Ouanes,corresponding author542 Sebastien Jochmans,corresponding author40 Jean-Emmanuel Alphonsine,40 Ly Van Vong,40 Nathalie Rolin,40 Oumar Sy,40 Jean Serbource-Goguel,40 Olivier Ellrodt,40 Mehran Monchi,40,597 Mabrouk Bahloul,corresponding author405 Turki Olfa,405 Benhamida Chokri,405 Hedi Chelly,406 Amelie Trichot,598 Gwenha?l Colin,corresponding author598 Isabelle Vinatier,246 Konstantinos Bachoumas,246,598 Jean-Claude Lacherade,246 Maud Fiancette,598 Aurelie Joret,598 Aihem Yehia,246,598 Matthieu Henry-Laguarrigue,246,598 Laurent Martin-Lefevre,598 Keyvan Razazi,corresponding author205 Mathieu Surenaud,599 Alexandre Bedet,184 Aurelien Seemann,184 Sophie H?e,600 Rapha?l Clere-Jehl,corresponding author500 Anne-Laure Charles,601 Bernard Geny,601 Pascal Bilbault,501 Simon Bourcier,corresponding author193 Gabriel Lejour,193 Simon Bourcier,corresponding author182,193 Pierre Yves Bo?lle,602 Nemlaghi Safaa,391 Sylvie Paulus,corresponding author603 Claire Flamens,603 Jean Neidecker,604 Jerome Rambaud,corresponding author605 Cecile Allioux,605 Romain Guedj,606 Isabelle Guellec,605,607 Julia Guilbert,605,607 Pierre-Louis Leger,605,607 Maryne Demoulin,605 Amelie Durandy,605 Sandrine Jean,605,607 Ricardo Carbajal,605,607 Aurelie Morand,608 Laurent Zieleskiewicz,609 Olivier Brissaud,610 Stephane Le Bel,611 Zoe Meresse,612 Michel Panuel,613 Laurent Thomachot,614 Marc Leone,615 Fabrice Michel,corresponding author614 Anna Deho’,corresponding author616,617 La?ly Sadozai,618 Stephane Dauger,616,617 Sonia Prot-Labarthe,618 Mathieu Genuini,corresponding author619 Moulin Florence,620 Jean-Marc Treluyer,621 Sylvain Renolleau,620,622,623 Emmanuelle Chalavon,96 Rodrigue Dessein,624 Bruno Grandbastien,14 Sarah Pesin,14 Francois Dubos,625 Stephane Leteurtre,corresponding author96 Marie-Aude Puel,corresponding author626 Marie Szulc,627 Anais Philippe,627 Francois Severac,628,629 Dominique Astruc,626 Pierre Kuhn,626 Philippe Desprez,630 Nabil Tabet Aoul,corresponding author631 Beno?t Colomb,corresponding author471 Anne Marie Petion,632 Laurent Queudet,632 Solenn Remy,corresponding author101 Mouaffak Youssef,corresponding author566 Nadia Roumeliotis,corresponding author633 Christian Dong,634 Geraldine Pettersen,633 Louis Crevier,635 Guillaume Emeriaud,633 Jer?me Naudin,corresponding author617 Laetitia Abdallah,617 Marion Ganier,617 Karine Frannais,617 Dylia Douglas,617 Cecile Flusin,617 David Brossier,corresponding author636 Redha Eltaani,637 Micha?l Sauthier,636 Bernard Guillois,638 Jerome Rambaud,corresponding author607 Michelle Larroquet,639 Alain Amblard,607 Noella Lode,640 Isabelle Casadevall,640 Katia Kessous,640 Herve Walti,607 Christophe Poire,534 Huixiong Chen,641 Bruno Megarbane,corresponding author642 A. M’rad,corresponding author473 Sahar Habacha,473 Bassem Chatbri,473 A. M’rad,corresponding author473 Cyril Masniere,534 Bruno Megarbane,corresponding author642 A. M’rad,corresponding author473 Samar Souissi,corresponding author536 Hatem El Ghord,643 N. Kouraichi,536 N. Brahmi,537 Takoua Marhbene,corresponding author444 Islam Mejri,644 Douha Lakhdar,645 Takoua T. Merhabane,644 He la Maamouri,corresponding author537 Oestreicher Charlotte,646 Helena Wegelius,646 Caroline Landelle,647 Jacques Schrenzel,648 Laurent Kaiser,648 Jer?me Pugin,corresponding author646 Hind Belhadj,corresponding author649 Paul Chanareille,corresponding author420 Adelie Ladureau,650 Alice Sanna,651 Amelie Rolle,650 Bertrand Pons,650 Pascale Piednoir,650 Fanny Ardisson,650 Frederic Martino,650 Thomas Bernos,650 Khalid Elkoun,650 Elie Elain,650 Roland Lawson,1 Matthieu Resh-Rigon,651 Sophie Belorgey,652 Guillaume Thiery,corresponding author650 Caroline Hauw Berlemont,corresponding author177 Cyprian Pricopi,653 Francoise Barthes,653 Thansya Doddie,corresponding author654 Mj Nsiala,655 Nh Situakibanza,656 Be Amisi,655 Mj Kazadi,657 Ma Kilembe,655 Christophe Clement,corresponding author658 Francois Lamontagne,659 Valerie Nocquet Boyer,646 Sebastien Naimo,646 Ronan Raulais,646 Emilie Genevois,646 Lucie Bouchoud,660 Filippo Boroli,184,646 Nour Abidi,646 Mohamed Abbas,648 Stefan Harbarth,647 Jer?me Pugin,corresponding author646 Pierre-Emmanuel Charles,corresponding author37 Caroline Dereux,506 Stanislas De Guillebon,corresponding author661 Eloise Morisse,662 Julie France,662 Deborah Gasser,662 Philippe Badia,662 Walter Picard,662 P. Corne,corresponding author262,263 I. De Boulastel,262 S. Seguin,262 A. Blasco,663 V. Ledur,664 Olivier Jonquet,262,263 Paktoris-Papine Sophie,82 Margaux Artiguenave,82 Faten El Sayed,665 Florence Espinasse,666 Aurelien Dinh,666 Cyril Charron,82 Benjamin Lebas,corresponding author375,377,378 Sophie Hatsch,375,377 Quentin Maestraggi,375,377 Anne-Florence Dureau,375 Francois Faitot,379 Dimitri Margetis,corresponding author563,667 Odile Bouvet,668 Didier Chevret,669 Erick Denamur,670,671 Justine Simonet,427 Philippe Vest,672 Vincent Peigne,corresponding author427 Severine Couffin,corresponding author673 M. Cheikh Bouhlel,674 Ahmed Khedher,674,675 Kaoula Meddeb,674 A. Azouzi,674 Y. Hamdaoui,674 Jihene Ayachi,674 W. Brahim,674 Rania Bouneb,674,676 Mohamed Boussarsar,corresponding author674 Nans Florens,140 Julie Vareon,140 Arnaud Malatray,140 Laurent Argaud,corresponding author140 Pierre Dupland,corresponding author677 Romain Vergier,678 Pauline Issaurat,678 Philippe Estagnasie,677,678 Pierre Squara,677,678 Alain Brusset,677,678 Vincent Genin,420 Ali Jendoubi,corresponding author679 Rifka Jlassi,679 Bassem Hamrouni,679 Yahia Marzougui,679 Jihen Kouka,679 Salma Ghedira,679 Mohamed Houissa,679 Kaouther Dhifaoui,572 Zied Hajjej,corresponding author572 Johanna Oziel,corresponding author160,351,680,681 Outcomerea Study Group, Alexy Tran Dinh,corresponding author179 Caroline Neulier,179 Marlene Amara,179 Nicaise Nebot,179 Gilles Troche,179 Nelly Breton,179 Sebastien Cavelot,179 Beatrice Pangon,179 Jacques Merrer,179 Francois Labaste,corresponding author682 Jean-Marie Conil,682 Julia Grossac,682 Stephanie Ruiz,682 Marion Grare,683 Vincent Minville,682 Bernard Georges,682 Guillaume Van Der Meersch,corresponding author160,351,681 Philippe Karoubi,351,352 Christophe Huang,351,352 Helene Carbonne,corresponding author684 Rishma Amarsy,685 Joaquim Mateo,111 Sophie Leloup Von Edelsberg,686 Christelle Vercheval,687 Pierre Damas,corresponding author686 Chaker Bouguerra,688 Noura Naas,572 Joris Muller,corresponding author689 Mickael Schaeffer,629 Pierre Tran Ba Loc,629 Stephanie Deboscker,689 Marie-Line Harley,378 Thierry Lavigne,689,690 Jennifer Brunet,corresponding author16,691 Bertrand Canoville,691 Francois Lellouche,692 Erwan L’her,83 Pierre Alexandre Bouchard,692 Mathieu Delorme,corresponding author693 Tamer Elfaramawy,694 Benoit Gosselin,694 Sarah Guegan,695 Jean-Bernard Michotte,corresponding author696 Enrico Staderini,697 Jonathan Dugernier,552,698 Rares Rusu,697 Giuseppe Liistro,699 Gregory Reychler,699 Mathieu Delorme,corresponding author693 Mathieu Simon,692 Elmaati Essoukaki,corresponding author475 Frederic Duprez,corresponding author437 Jean Bernard Michotte,700 Olivier Contal,700 Becem Trabelsi,572 Zied Hajjej,corresponding author572 Hedi Garsallah,572 Zied Hajjej,corresponding author572 Khaoula Harira,572 Cedric Rafat,701 Eric Mariotte,corresponding author57,164 Caroline Le Jeune,corresponding author702 Pascal Roy,703 Mauricette Michallet,702 Yoann Zerbib,corresponding author147 Francois Baudin,704 Francois Blot,705,706 Caroline Bornstain,354 Stephanie Gelinotte,707 Jean-Philippe Rigaud,707 Fabienne Tamion,corresponding author2,446,708 Marie Bouteloup,709 Micha?l Darmon,corresponding author329 Groupe de Recherche en Reanimation Respiratoire et Onco-Hematologique (GRRROH), H. Nouira,674 Julie Boisrame-Helms,correspondin

Publish date

2016

PMID

30215677

Abstract

Background
A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks (Q4W) has been approved in several markets, including the United States, Canada, and European Union, as an alternative dosing regimen for several indications. Approvals of this Q4W regimen were based on population pharmacokinetic (PK) analyses, established flat exposure-response relationships, and clinical safety. The objective of this study was to compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W regimen.

Patients and methods
Nivolumab PK exposure for the 480 mg Q4W schedule was simulated for 3817 patients across multiple tumor types and compared with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. The safety profile of the Q4W schedule was assessed by analysis of clinical data from 61 patients who transitioned to nivolumab 480 mg Q4W from 3 mg/kg Q2W during four phase III clinical trials.

Results
Compared with 3 mg/kg Q2W, nivolumab 480 mg Q4W produced similar time-averaged concentration, approximately 16% lower trough concentration, and 45% higher peak concentration at steady state. The peak concentration for 480 mg Q4W was significantly lower than that of 10 mg/kg Q2W, a dose previously shown to have an acceptable tolerability and safety profile. Treatment-related adverse events (TRAEs) that started after transitioning from 3 mg/kg Q2W to 480 mg Q4W were reported in 14.8% of patients, with 1.6% of patients reporting grades 3-4 TRAEs. Pooled safety data for these patients are consistent with those for the 3 mg/kg Q2W schedules, and no new safety signals were identified.

Conclusions
The time-averaged steady-state exposure and safety profile of nivolumab 480 mg Q4W are consistent with that of 3 mg/kg Q2W across multiple tumor types. Nivolumab 480 mg Q4W represents a new dosing schedule option, and in addition to 240 mg Q2W, provides convenience and flexibility for patient care.

Clinical trial numbers
NCT01721772, NCT01668784, NCT01673867, NCT01642004

KEYWORDS

nivolumab, Q4W, PK exposure, safety, immuno-oncology, solid tumors

Title

Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer

Author

G V Long,1,2,3 S S Tykodi,4,5 J G Schneider,6 C Garbe,7 G Gravis,8,9,10 M Rashford,11 S Agrawal,11 E Grigoryeva,11 A Bello,12 A Roy,12 L Rollin,13 and X Zhao12

Publish date

2018 Nov