Brivaracetam Population Pharmacokinetics and Exposure-Response Modeling in Adult Subjects With Partial-Onset Seizures

Journal of Clinical Pharmacology

Volumn 56, Issue 12, 2016, Pages 1591-1602

  Schoemaker, Rik ^a,b   Wade, Janet R ^a,b   Stockis, Armel ^c  

^a Exprimo NV   (Belgium)

^b Present affiliation: Occams   (Netherlands)

^c UCB PHARMA   (Belgium)

Author keywords

brivaracetam; concentration effect relationship; daily seizure counts; epilepsy; nonlinear mixed effects modeling; nonmem; SV2A

Indexed keywords

BENZODIAZEPINE; BENZODIAZEPINE DERIVATIVE; BRIVARACETAM; CARBAMAZEPINE; LAMOTRIGINE; LEVETIRACETAM; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PRIMIDONE; TOPIRAMATE; VALPROIC ACID; 2 PYRROLIDONE DERIVATIVE; ANTICONVULSIVE AGENT;

ADULT; AGED; ALLOMETRY; ARTICLE; BINOMIAL DISTRIBUTION; BODY WEIGHT; CLEARANCE; COMPARTMENT MODEL; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; FEMALE; FOCAL EPILEPSY; HUMAN; MAJOR CLINICAL STUDY; MALE; SIMULATION; TREATMENT RESPONSE; BIOLOGICAL MODEL; CLINICAL TRIAL; DOSE RESPONSE; EPILEPSIES, PARTIAL; METABOLISM; MIDDLE AGED; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; SEIZURES; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTICONVULSANTS; DOSE-RESPONSE RELATIONSHIP, DRUG; EPILEPSIES, PARTIAL; FEMALE; HUMANS; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PYRROLIDINONES; SEIZURES;

EID: 84994416022     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.761     Document Type: Article

References (25)

1. Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78:1548–1554.
2. Brodie MJ, Schachter SC, Kwan P. Fast Facts. Epilepsy, 5th ed. Oxford, UK: Health Press; 2012.
3. Lynch BA, Lambeng N, Nocka K, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Nat Acad Sci. 2004;101:9861–9866.
4. French JA, Costantini C, Brodsky A, von Rosenstiel P. Adjunctive brivaracetam for refractory partial-onset seizures. A randomized, controlled trial. Neurology. 2010;75:519–525.
5. van Paesschen W, Hirsch E, Johnson M, Falter U, von Rosenstiel P. Efficacy and tolerability of adjunctive brivaracetam in adults with uncontrolled partial-onset seizures: a phase IIb, randomized, controlled trial. Epilepsia. 2013;54:89–97.
6. Biton V, Berkovic SF, Abou-Khalil B, et al. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55:57–66.
7. Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, Lu S. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014;55:47–56.
8. Klein P, Schiemann J, Sperling MR, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015;56:1890–1898.
9. Rolan P, Sargentini-Maier ML, Pigeolet E, Stockis A. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 2008;66:71–75.
10. Sargentini-Maier ML, Rolan P, Connell J, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males. Br J Clin Pharmacol. 2007;63:680–688.
11. Sargentini-Maier ML, Espié P, Coquette A, Stockis A. Pharmacokinetics and metabolism of [14C]-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab Dispos. 2008;36:36–45.
12. Sargentini-Maier ML, Sokalski A, Boulanger P, Jacobs T, Stockis A. Brivaracetam disposition in renal impairment. J Clin Pharmacol. 2012;52:1927–1933.
13. Beal SL, Sheiner LB, Boeckmann AJ, Bauer RJ, eds. NONMEM Users Guides. Ellicott City, MD: Icon Development Solutions; 1989–2009.
14. Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit—a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed. 2005;79:241–257.
15. R Development Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2007. http://www.R-project.org.
16. Anderson BJ, Holford NHG. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303–332.
17. Lewis S, Clarke M. Forest plots: trying to see the wood and the trees. Br Med J. 2001;322:1479–1480.
18. Jonsson EN, Karlsson MO. Automated covariate model building within NONMEM. Pharm Res. 1998;15:1463–1468.
19. Tunblad K, Lindbom L, McFadyen L, Jonsson EN, Marshall S, Karlsson MO. The use of clinical irrelevance criteria in covariate model building with application to dofetilide pharmacokinetic data. J Pharmacokinet Pharmacodyn. 2008;35:503–526.
20. Karlsson MO, Holford N. A tutorial on visual predictive checks. 2008. Abstract 1434. www.page-meeting.org/?abstract=1434.
21. Plan EL. Modeling and simulation of count data. CPT Pharmacometr Syst Pharmacol. 2014;3:e129.
22. Troconiz IF, Plan EL, Miller R, Karlsson MO. Modelling overdispersion and Markovian features in count data. J Pharmacokinet Pharmacodyn. 2009;36:461–477.
23. Ahn JE, Plan EL, Karlsson MO, Miller R. Modeling longitudinal daily seizure frequency data from pregabalin add-on treatment. J Clin Pharmacol. 2012;52:880–892.
24. Petersson KJ, Hanze E, Savic RM, Karlsson MO. Semiparametric distributions with estimated shape parameters. Pharm Res. 2009;26:2174–2185.
25. Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs)—Part 1: pharmacokinetic and pharmacodynamic interactions between AEDs. Clin Pharmacokinet. 2013;52:927–966.