Lidocaine as treatment for neonatal seizures: Evaluation of previously developed population pharmacokinetic models and dosing regimen.
clinical pharmacology
drug utilization
mass spectrometry
modelling and simulation
neonatology
pharmacometrics
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
26
07
2019
revised:
08
09
2019
accepted:
10
09
2019
pubmed:
31
10
2019
medline:
29
7
2021
entrez:
31
10
2019
Statut:
ppublish
Résumé
Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were assessed. Data from preterm neonates and (near-)term neonates with and without therapeutic hypothermia receiving lidocaine were included. Pharmacokinetic analyses were performed using non-linear mixed effects modelling. Simulations were performed to evaluate the proposed dosing regimen. Lidocaine was considered effective if no additional anticonvulsant was required and safe if no cardiac adverse events occurred. Data were available for 159 neonates; 50 (31.4%) preterm and 109 term neonates, of whom 49 (30.8%) were treated with therapeutic hypothermia. Lidocaine clearance increased with postmenstrual age by 0.69%/day (95% confidence interval 0.54-0.84%). During therapeutic hypothermia (33.5°C), lidocaine clearance was reduced by 21.8% (7.26%/°C, 95% confidence interval 1.63-11.2%) compared to normothermia (36.5°C). Simulations demonstrated that the proposed dosing regimen leads to adequate average lidocaine plasma concentrations. Effectiveness and safety were assessed in 92 neonates. Overall effectiveness was 53.3% (49/92) and 56.5% (13/23) for neonates receiving the proposed dosing regimen. No cardiac toxicity was observed. Lidocaine pharmacokinetics was adequately described across the entire neonatal age range. With the proposed dosing regimen, lidocaine can provide effective and safe treatment for neonatal seizures.
Identifiants
pubmed: 31663153
doi: 10.1111/bcp.14136
pmc: PMC6983510
doi:
Substances chimiques
Anticonvulsants
0
Lidocaine
98PI200987
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-84Subventions
Organisme : ZonMw
ID : 40-41500-98-900
Pays : International
Organisme : ZonMw
ID : 40-41500-98-9002
Pays : International
Informations de copyright
© 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Clin Pharmacol Ther. 2018 Mar;103(3):458-467
pubmed: 28555724
Circulation. 2018 Dec 4;138(23):e740-e749
pubmed: 30571262
CPT Pharmacometrics Syst Pharmacol. 2013 Jun 26;2:e50
pubmed: 23836189
Acta Paediatr. 2013 Sep;102(9):863-7
pubmed: 23738612
Pediatrics. 2006 Mar;117(3):843-50
pubmed: 16510666
Acta Paediatr Scand. 1988 Jan;77(1):79-84
pubmed: 3369308
Circulation. 2018 Dec 4;138(23):e731-e739
pubmed: 30571264
Br J Clin Pharmacol. 2020 Jan;86(1):75-84
pubmed: 31663153
Pediatrics. 2019 Jan;143(1):
pubmed: 30587535
PLoS One. 2019 Mar 14;14(3):e0213537
pubmed: 30870445
Circulation. 1971 Feb;43(2):205-11
pubmed: 5540706
Eur J Pediatr. 2004 Nov;163(11):637-41
pubmed: 15309624
BMC Pediatr. 2012 May 22;12:45
pubmed: 22515424
Cochrane Database Syst Rev. 2013 Jan 31;(1):CD003311
pubmed: 23440789
J Clin Pharmacol. 2018 Oct;58 Suppl 10:S10-S25
pubmed: 30248190
Neonatology. 2015;108(2):130-6
pubmed: 26111505
Eur J Pediatr. 2006 Sep;165(9):598-604
pubmed: 16691409
Dev Med Child Neurol. 2019 Jun;61(6):661-666
pubmed: 30714130
J Matern Fetal Neonatal Med. 2018 Aug;31(16):2175-2182
pubmed: 28573895
Pediatr Res. 2011 Nov;70(5):535-40
pubmed: 21796017
Drugs. 2016 Apr;76(6):647-61
pubmed: 26943929
Paediatr Drugs. 2017 Dec;19(6):553-567
pubmed: 28770451
Int Endod J. 2019 Jun;52(6):779-789
pubmed: 30638269
Pediatrics. 2010 Feb;125(2):e358-66
pubmed: 20100767
Pediatr Nephrol. 2009 Jan;24(1):67-76
pubmed: 18846389
Neurology. 2002 Feb 26;58(4):542-8
pubmed: 11865130
Neonatology. 2013;104(1):15-21
pubmed: 23615314
Eur J Pharm Sci. 2016 Sep 20;92:117-30
pubmed: 27373670
J Pharmacokinet Pharmacodyn. 2001 Oct;28(5):481-504
pubmed: 11768292
Epilepsia. 2016 Feb;57(2):233-42
pubmed: 26719344
J Pharm Sci. 2013 Sep;102(9):2941-52
pubmed: 23650116
Pediatrics. 2006 Apr;117(4):1270-80
pubmed: 16585324
PLoS One. 2019 Feb 14;14(2):e0211910
pubmed: 30763356
Neurology. 2007 Nov 6;69(19):1816-22
pubmed: 17984448
J Child Neurol. 2014 Jan;29(1):31-5
pubmed: 23271754
J Pediatr. 2011 Nov;159(5):731-735.e1
pubmed: 21839470
Arch Dis Child Fetal Neonatal Ed. 2013 Jul;98(4):F341-5
pubmed: 23303304
Pediatr Res. 2012 Aug;72(2):186-93
pubmed: 22580721
Clin Pharmacokinet. 2010 May;49(5):277-94
pubmed: 20384391
Antimicrob Agents Chemother. 2018 Mar 27;62(4):
pubmed: 29378710
J Pharmacokinet Pharmacodyn. 2016 Dec;43(6):583-596
pubmed: 27730482
N Engl J Med. 1974 Dec 19;291(25):1324-6
pubmed: 4610392
J Pediatr. 2009 Sep;155(3):318-23
pubmed: 19540512
N Engl J Med. 2003 Sep 18;349(12):1157-67
pubmed: 13679531
J Neonatal Perinatal Med. 2019;12(2):117-125
pubmed: 30814366
Neurology. 2007 Dec 4;69(23):2177-85
pubmed: 18056582
Clin Pharmacokinet. 2011 Jul;50(7):461-9
pubmed: 21651313
Neurology. 2000 Aug 22;55(4):506-13
pubmed: 10953181
N Engl J Med. 1967 Dec 7;277(23):1215-9
pubmed: 4862377
Acta Paediatr. 1992 Jan;81(1):35-9
pubmed: 1600301
J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jan 15;881-882:111-4
pubmed: 22192875
Basic Res Cardiol. 1998;93 Suppl 1:125-32
pubmed: 9833140