Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data

British Journal of Clinical Pharmacology
Z Hussein, J Posner

Abstract

To examine the population pharmacokinetics of lamotrigine in patients newly diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48 weeks. The population consisted of 158 Caucasians and 5 Asians of whom 81 were males and 82 females. Age and weight ranged between 14 and 76 years and 41-107 kg, respectively. A one-compartment compartment model with first-order absorption and elimination was fitted to plasma lamotrigine concentration-time profiles from retrospective drug monitoring, using non-linear mixed effect modelling (NONMEM), with first-order estimation. Oral clearance (CLo), apparent volume of distribution (V/F) and absorption rate constant (Ka) were the main pharmacokinetic parameters. CLo was not significantly influenced by body weight, age, gender, oral contraceptives and dose. However, due to auto-induction CLo increased by 17.3% during the 48 weeks of therapy, from 1.94 to 2.28 l h(-1), and was 28.7% lower in Asians than Caucasian. The final magnitude in interpatient variability was 32%. The effect of the covariates weight, age, race and gender on V/F was examined and none was statistically significant. The final population estimate of V/F was 77.4 l with an interpatient variability of 34%. In v...Continue Reading

Citations

Aug 4, 2009·European Journal of Drug Metabolism and Pharmacokinetics·Mladena LalicMomir Mikov
Jul 28, 2006·European Journal of Clinical Pharmacology·A M AlmeidaM M Caramona
Dec 25, 2012·European Journal of Clinical Pharmacology·Noppaket SingkhamBaralee Punyawudho
Feb 9, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Arne ReimersEirik Sundby
May 4, 2013·Clinical Pharmacokinetics·Domenico Italiano, Emilio Perucca
Oct 30, 2012·Acta Pharmacologica Sinica·Da-ke HeHai-tao Liu
Apr 12, 2003·Epilepsia·David V LardizabalMaria Del Mar Carreño
Nov 9, 2002·American Journal of Therapeutics·Ehab S EL DesokyHartmut Derendorf
Oct 26, 1999·Epilepsia·F Matsuo
Apr 10, 1999·Journal of Clinical Pharmacology·T H GraselaC Chen
Apr 3, 2012·Biological & Pharmaceutical Bulletin·Yoshiaki YamamotoYoshiyuki Kagawa
Dec 4, 2004·Clinical Chemistry and Laboratory Medicine : CCLM·Hugo M NeelsWilly E Lambert
Oct 20, 2006·Clinical Pharmacokinetics·Svein I Johannessen, Torbjörn Tomson
Jul 2, 2008·Paediatric Drugs·Allison M Chung, Lea S Eiland
Nov 19, 2013·European Journal of Clinical Pharmacology·Branka BrzakovićMilena Pokrajac
Jun 5, 2012·European Journal of Clinical Pharmacology·Surulivelrajan MallaysamyDevarakonda Ramakrishna
Dec 11, 2014·European Journal of Drug Metabolism and Pharmacokinetics·Arne ReimersEylert Brodtkorb
Jul 20, 2010·Pharmaceuticals·Matthew D Krasowski
Jun 14, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Matthew D Krasowski, Gwendolyn A McMillin
Apr 28, 2005·Expert Review of Neurotherapeutics·Jonathan FungLakshmi N Yatham
Dec 6, 2006·Expert Review of Neurotherapeutics·Sheetal MalikLawrence J Hirsch
Apr 14, 2006·Expert Opinion on Drug Safety·Howard H FennBrian Alldredge
Sep 15, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Hee-Jung KimSeung Bong Hong
Nov 9, 2011·Advanced Drug Delivery Reviews·Cecilie Johannessen LandmarkTorbjörn Tomson
Aug 17, 2010·Epilepsy & Behavior : E&B·Torbjörn TomsonInger Ohman
Jun 23, 2009·Progress in Neuro-psychopharmacology & Biological Psychiatry·Young Sup WooKyung Joon Min
Mar 21, 2008·Psychosomatics·Jessica R OesterheldNeil B Sandson
Oct 19, 2006·Epilepsia·Ilo E Leppik
Feb 26, 2008·Journal of Clinical Pharmacology·Baralee PunyawudhoAngela K Birnbaum
May 16, 2012·Journal of Clinical Pharmacy and Therapeutics·B B BrzakovićM Š Prostran
Jan 6, 2010·Acta Neurologica Scandinavica·L AlmeidaP Soares-da-Silva
Jun 3, 2014·Annals of Clinical and Translational Neurology·Akshanth R PolepallyAngela K Birnbaum
Jul 15, 2006·Epilepsy & Behavior : E&B·Magdalena SzaflarskiRonnie D Horner
Jul 15, 2005·Expert Opinion on Pharmacotherapy·Zubin Bhagwagar, Guy M Goodwin

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