Population pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator

Journal of Pharmacokinetics and Pharmacodynamics

Volumn 41, Issue 3, 2014, Pages 261-278

  Krause, Andreas ^a   Brossard, Patrick ^a   D'Ambrosio, Daniele ^a   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

Author keywords

Circadian variation; Indirect effect model; Population pharmacokinetics pharmacodynamics; Total lymphocyte count

Indexed keywords

PLACEBO; PONESIMOD; SPHINGOSINE 1 PHOSPHATE RECEPTOR; THIAZOLE DERIVATIVE;

ADOLESCENT; ADULT; AGED; ARTICLE; CIRCADIAN RHYTHM; DRUG ABSORPTION; DRUG EFFECT; DRUG ELIMINATION; FEMALE; HUMAN; HUMAN CELL; LYMPHOCYTE; MALE; PRIORITY JOURNAL; BODY WEIGHT; DRUG EFFECTS; INTESTINE ABSORPTION; LYMPHOCYTE COUNT; METABOLISM; MIDDLE AGED; MULTIPLE SCLEROSIS; PHYSIOLOGY; POPULATION; STATISTICAL MODEL; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; BODY WEIGHT; CIRCADIAN RHYTHM; FEMALE; HUMANS; INTESTINAL ABSORPTION; LYMPHOCYTE COUNT; MALE; MIDDLE AGED; MODELS, STATISTICAL; MULTIPLE SCLEROSIS; POPULATION; RECEPTORS, LYSOSPHINGOLIPID; THIAZOLES; YOUNG ADULT;

EID: 84904187975     PISSN: 1567567X     EISSN: 15738744     Source Type: Journal    
DOI: 10.1007/s10928-014-9362-4     Document Type: Article

References (31)

1. Piali L, Froidevaux S, Hess P, Nayler O, Bolli MH, Schlosser E, Kohl C, Steiner B, Clozel M (2011) The selective sphingosine 1-phosphate receptor 1 agonist ponesimod protects against lymphocyte-mediated tissue inflammation. J Pharmacol Exp Ther 337(2):547-556. doi:10.1124/jpet.110.176487
2. Brossard P, D'Ambrosio D, Cavallaro M, Dingemanse J (2010) Differential effects of ACT-128800, a selective S1P1 receptor agonist, on blood-circulating human T-lymphocyte subpopulations. Poster presented at the 111th Am Soc Clin Pharmacol Ther (ASCPT) meeting, Atlanta, GA, 17-20 March, 2010 Poster PIII-82. Clin Pharmacol Ther 87(S1):S56
3. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427(6972):355-360. doi:10.1038/nature02284 (Pubitemid 38133663)
4. Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG (2005) Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309(5741):1735-1739. doi:10.1126/science.1113640 (Pubitemid 41285945)
5. Brossard P, Derendorf H, Xu J, Maatouk H, Halabi A, Dingemanse J (2013) Pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P receptor modulator, in the first-in-human study. Br J Clin Pharmacol 76(6):888-896. doi:10.1111/bcp.12129
6. Brossard P, Scherz M, Halabi A, Maatouk H, Krause A, Dingemanse J (2014) Multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an S1P receptor modulator: favorable impact of dose up-titration. J Clin Pharmacol 54(2):179-188. doi:10.1002/jcph.244
7. Reyes M, Brossard P, Chassard D, Hoch M, Dingemanse J (2014) Effects of ponesimod, a selective S1P1 receptor modulator, on the pharmacokinetics of a hormonal combination contraceptive. Eur J Clin Pharmacol 70(3):287-293. doi:10.1007/s00228-013-1625-2
8. Brossard P, D'Ambrosio D, Murat I, Dingemanse J (2012) Effects of three different up-titration regimens of ponesimod, a selective S1P1 receptor agonist, on heart rate. Poster presented at the 113th Am Soc Clin Pharmacol Ther (ASCPT) Meeting, National Harbor, MD, 14-17 March, 2012 Poster PII-109. Clin Pharmacol Ther 91(S1):S92-S93
9. Vaclavkova A, Brossard P, Cavallaro M, D'Ambrosio D, Nacarino Martinez A, Morganti A, Pirron U, Schmidt A-G, Zhang-Fu W (2011) AC-058A200: Multicenter, randomized, double-blind, placebo-controlled, Phase IIa study to evaluate the efficacy, safety, and tolerability of ACT-128800, an S1P1 receptor agonist, administered for 6 weeks to subjects with moderate to severe chronic plaque psoriasis. Pubmed. http://www.clinicaltrials.gov/ct2/show/NCT00852670
10. Holford NH Absorption models using NM-TRAN. http://holford.fmhs.auckland. ac.nz/docs/absorption-processes.pdf
11. Holford NH, Ambros RJ, Stoeckel K (1992) Models for describing absorption rate and estimating extent of bioavailability: application to cefetamet pivoxil. J Pharmacokinet Biopharm 20(5):421-442 (Pubitemid 23034408)
12. Braude S, Beck A (2013) Complete blood counts with differential: more accurate reference ranges based on circadian leukocyte trafficking. J Clin Pathol 66(11):909-910. doi:10.1136/jclinpath-2013-201776
13. Kirsch S, Thijssen S, Alarcon Salvador S, Heine GH, van Bentum K, Fliser D, Sester M, Sester U (2012) T-cell numbers and antigen-specific T-cell function follow different circadian rhythms. J Clin Immunol 32(6):1381-1389. doi:10.1007/s10875-012-9730-z
14. Fisher LE, Ludwig EA, Jusko WJ (1992) Pharmacoimmunodynamics of methylprednisolone: trafficking of helper T lymphocytes. J Pharmacokinet Biopharm 20(4):319-331 (Pubitemid 23034402)
15. Holford NH (2012) An introduction to visual predictive checks. http://holford.fmhs.auckland.ac.nz/docs/vpc-tutorial-and-datatop.pdf
16. Karlsson MO (2008) A tutorial on visual predictive checks. http://www.page-meeting.org/?abstract=1434
17. SAS Institute Inc. (2006) Base SAS 9.1.3 procedures guide. SAS Institute Inc., Cary
18. R Development Core Team (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
19. Beal SL, Sheiner LB (1989-1998) NONMEM users guides. Icon Development Solutions, Ellicott City
20. Free Software Foundation (2009) GNU Fortran. http://gcc.gnu.org/fortran/
21. Metrum Institute (2008) NMQual: A software environment for operating NONMEM. https://code.google.com/p/nmqual/
22. Savic RM, Karlsson MO (2009) Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions. AAPS J 11(3):558-569. doi:10.1208/s12248-009-9133-0
23. Hoch M, D'Ambrosio D, Wilbraham D, Dingemanse J (2013) Uptitration study with ponesimod, a selective S1P1 receptor modulator, to assess its maximum tolerated dose in healthy subjects. Oral contribution OC015 presented at the 11th Conference of the European Association for Clinical Pharmacology and Therapeutics (EACPT), Geneva, Switzerland, August 28-31, 2013. Clin Ther 35(8S):e6-e7
24. Francis G, Kappos L, O'Connor P, Collins W, Tang D, Mercier F, Cohen J (2013) Temporal profile of lymphocyte counts and relationship with infections with fingolimod therapy. Mult Scler 20(4):471-480. doi:10.1177/1352458513500551
25. Mehling M, Johnson TA, Antel J, Kappos L, Bar-Or A (2011) Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 76(8 Suppl 3):S20-S27. doi:10.1212/WNL. 0b013e31820db341
26. Kasper LH, Shoemaker J (2010) Multiple sclerosis immunology: the healthy immune system vs the MS immune system. Neurology 74(Suppl 1):S2-S8. doi:10.1212/WNL.0b013e3181c97c8f
27. Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, Groenewegen A, Vitaliti A, Sing T, Luttringer O, Yang J, Gardin A, Wang N, Crumb WJ Jr, Saltzman M, Rosenberg M, Wallstrom E (2012) The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol 167(5):1035-1047. doi:10.1111/j.1476-5381.2012.02061. x
28. Mehling M, Brinkmann V, Antel J, Bar-Or A, Goebels N, Vedrine C, Kristofic C, Kuhle J, Lindberg RL, Kappos L (2008) FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology 71(16):1261-1267. doi:10.1212/01.wnl.0000327609.57688.ea
29. Henault D, Galleguillos L, Moore C, Johnson T, Bar-Or A, Antel J (2013) Basis for fluctuations in lymphocyte counts in fingolimod-treated patientswithmultiple sclerosis. Neurology 81(20):1768-1772. doi:10.1212/01.wnl. 0000435564.92609.2c
30. Hoch M, Vaclavkova A, Stoltz R, Brossard P, Dingemanse J (2013) Thorough QT study with ponesimod, a selective S1P1 receptor modulator. Poster PP162 presented at the 11th Conference of the European Association for Clinical Pharmacology and Therapeutics (EACPT), Geneva, Switzerland, August 28-31, 2013. Clin Ther 35(8S):e68-e69
31. Vaclavkova A, Chimenti S, Arenberger P, Holló P, Sator P-G, Burcklen M, Stefani M, D'Ambrosio D (2014) A multicentre, randomised, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy, safety and tolerability of ponesimod, an oral sphingosine 1-phosphate receptor-1 modulator, in patients with chronic plaque psoriasis. Lancet (to appear)