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Journal of Pharmacy Practice
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Pharmacokinetic Properties of New Antiepileptic Drugs

Michele Y. Splinter, PharmD, MS

College of Pharmacy, Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190michele-splinter{at}ouhsc.edu; Department of Pharmacy, Clinical and Administrative Sciences at the College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City

Eight new antiepileptic drugs (AEDs) have been approved for use within the United States within the past decade. They are felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide. These afford clinicians with more options to increase efficacy and tolerability in the treatment of patients with epilepsy. Pharmacokinetic properties and drug interactions with other AEDs and other medications taken for comorbidities are individually discussed for each of these new agents. Drug concentrations are not routinely monitored for these newer agents, and there have been few studies designed to investigate their concentration-effect relationships. For most of these medications, the concentrations observed in responders and nonresponders overlap considerably and levels associated with efficacy are often associated with adverse events, complicating the definition of target ranges. Also, epilepsy manifests itself sporadically causing difficulty in clinically monitoring efficacy of medications. Therapeutic drug monitoring provides for the individualization of treatment for these agents, which is important because they demonstrate significant variability in inter- and intraindividual pharmaco-kinetic properties. Therapeutic drug monitoring also allows for identification of noncompliance, drug interactions, and toxicity. Current knowledge of the relationships between efficacy, toxicity, and drug concentrations is discussed.

Key Words: Antiepileptic therapy • pharmacokinetics • therapeutic drug monitoring • drug interactions

References

  • Perucca E. Marketed new antiepileptic drugs: are they better than old-generation agents? Ther Drug Monitor. 2002;24:74-80.[CrossRef][Medline] [Order article via Infotrieve]
  • Bourgeois BFD. Pharmacokinetic properties of current antiepileptic drugs: what improvements are needed? Neurology. 2000;55:S11-S16.
  • Gidal BE. Pharmacokinetics of the new antiepileptic drugs. Am J Managed Care. 2001;7(Suppl):S216-S220.
  • Glauser TA, Pippenger CE. Controversies in blood-level monitoring: reexamining its role in the treatment of epilepsy. Epilepsia. 2000;41(Suppl 8):S6-S15.
  • Arryoyo S, Kramer G. Treating epilepsy in the elderly. Drug Safety. 2001;24:991-1015.[Medline] [Order article via Infotrieve]
  • Splinter MY. Epilepsy in the female patient: new pharmacotherapy and gender-related issues. Female Patient. 2002;27: (Primary Care Ed) 33-39, (OB/GYN Ed) 32-39.
  • French J. Use of levetiracetam in special populations. Epilepsia. 2001;42(Suppl 4);40-43.
  • Tomson T, Johannessen SI. Therapeutic monitoring of the new antiepileptic drugs. Eur J Clin Pharmacol. 2000;55:697-705.[Medline] [Order article via Infotrieve]
  • Johannessen SI, Battino D, Berry DJ, et al. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther Drug Monit. 2003;25:347-363.[Medline] [Order article via Infotrieve]
  • Kelley MT, Walson PD, Cox S, Dusci LJ. Population pharmacokinetics of felbamate in children. Ther Drug Monit. 1997;19:29-36.[CrossRef][Medline] [Order article via Infotrieve]
  • Theodore WH. Felbamate. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippencott-Raven; 1998:1509-1514.
  • Pellock JM. Felbamate. Epilepsia. 1999;40(Suppl 5):S57-S62.
  • Gram L. Pharmacokinetics of new antiepileptic drugs. Epilepsia. 1996;37(Suppl 6):S12-S16.
  • Hachad H, Ragueneau-Majlessi I, Levy RH. New antiepileptic drugs: review on drug interactions. Ther Drug Monit. 2002;24:91-103.[CrossRef][Medline] [Order article via Infotrieve]
  • Glue P, Sulowicz W, Colucci R, et al. Single-dose pharmacokinetics of felbamate in patients with renal dysfunction. Br J Clin Pharmacol. 1997;44:91-93.[Medline] [Order article via Infotrieve]
  • Perucca E. The clinical pharmacokinetics of the new antiepileptic drugs. Epilepsia. 1999;40(Suppl 9):S7-S13.
  • The felbamate study group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med. 1993;328:29-33.[Abstract/Free Full Text]
  • Harden CL, Trifiletti R, Kutt H. Felbamate levels in patients with epilepsy. Epilepsia. 1996;37:280-283.[CrossRef][Medline] [Order article via Infotrieve]
  • Troupin AS, Montouris G, Hussein G. Felbamate: therapeutic range and other kinetic information. J Epilepsy. 1997;10:26-31.[CrossRef]
  • Perucca E. Is there a role for therapeutic drug monitoring of new anticonvulsants? Clin Pharmacokinet. 2000;38:191-204.[Medline] [Order article via Infotrieve]
  • Morris GL. Gabapentin. Epilepsia. 1999;40(Suppl 5):S63-S70.
  • Haig GM, Bockbrader HN, Wesche DL, et al. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 2001;41:507-514.[Abstract]
  • Goa KL, Sorkin EM. Gabapentin: a review of its pharmacological properties and clinical potential in epilepsy. Drugs. 1993;43:409-427.
  • Ouellet D, Bockbrader HN, Wesche DL, Shapiro DY, Garofalo E. Population pharmacokinetics of gabapentin in infants and children. Epilepsy Res. 2001;47:229-241.[CrossRef][Medline] [Order article via Infotrieve]
  • McLean MJ. Clinical pharmacokinetics of gabapentin. Neurology. 1994;44(Suppl 5):S17-S22.[Medline] [Order article via Infotrieve]
  • Berry DJ, Beran RG, Plunkeft MJ, Clarke LA, Hung WT. The absorption of gabapentin following high dose escalation. Seizure. 2003;12:28-36.[CrossRef][Medline] [Order article via Infotrieve]
  • Boyd RA, Türck D, Abel RB, Sedman AJ, Bockbrader HN. Effects of age and gender on single-dose pharmacokinetics of gabapentin. Epilepsia. 1999;40:474-479.[CrossRef][Medline] [Order article via Infotrieve]
  • Gidal BE, Radulovic LL, Kruger S, Rutecki P, Pitterle M, Bockbrader HN. Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability. Epilepsy Res. 2000;40:123-127.[CrossRef][Medline] [Order article via Infotrieve]
  • Wilson EA, Sills GJ, Forrest G, Brodie MJ. High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients. Epilepsy Res. 1998;29:161-166.[Medline] [Order article via Infotrieve]
  • Muscas GC, Chiroli S, Luceri F, Del Mastio, M, Balestrieri F, Arnetoli G. Conversion from thrice daily to twice daily administration of gabapentin (GBP) in partial epilepsy: analysis of clinical efficacy and plasma levels. Seizure. 2000;9:47-50.[Medline] [Order article via Infotrieve]
  • Chan V, Morris RG, Ilett K, Tett SE. Population pharmacokinetics of lamotrigine. Ther Drug Monit. 2001;23:630-635.[CrossRef][Medline] [Order article via Infotrieve]
  • GlaxoSmithKline. Lamictal package insert. Research Triangle Park, NC: GlaxoSmithKline; 2003.
  • Birnbaum AK, Kriel RL, Im Y, Remmel RP. Relative bioavailability of lamotrigine chewable dispersible tablets administered rectally. Pharmacotherapy. 2001;21:158-162.[Medline] [Order article via Infotrieve]
  • Armijo JA, Bravo J, Cuadrado A, Herranz JL. Lamotrigine serum concentration-to-dose ratio: influence of age and concomitant antiepileptic drugs and dosage implications. Ther Drug Monit. 1999;21:182-190.[CrossRef][Medline] [Order article via Infotrieve]
  • Chen C. Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children. Br J Clin Pharmacol. 2000;50:135-145.[Medline] [Order article via Infotrieve]
  • Tran TA, Leppick IE, Blesi K, Sathanandan ST, Remmel R. Lamotrigine clearance during pregnancy. Neurology. 2002;59:251-255.[Abstract/Free Full Text]
  • Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate and during lactation. Epilepsia. 2000;41:709-713.[CrossRef][Medline] [Order article via Infotrieve]
  • Morris RG, Black AB, Harris AL, Batty AB, Sallustio BC. Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Br J Clin Pharmacol. 1998:46:547-551.[Medline] [Order article via Infotrieve]
  • Böttiger Y, Svensson JO, Ståhle L. Lamotrigine drug interactions in a TDM material. Ther Drug Monit. 1999;21:171-174.[CrossRef][Medline] [Order article via Infotrieve]
  • Chong E, Dupuis LL. Therapeutic drug monitoring of lamotrigine. Ann Pharmacother. 2002;36:917-919.[Abstract]
  • Shorvon SD, van Rijckevorsel K. A new antiepileptic drug: levetiracetam, a pyrrolidone recently licensed as an antiepileptic drug. J Neurol Neurosurg Psychiatry. 2002;72:426-429.[Free Full Text]
  • Radtke RA. Pharmacokinetics of levetiracetam. Epilepsia. 2001;42(Suppl 4):24-27.
  • Wheless JW. Using the new antiepilepsy drugs in children. J Child Neurol. 2002;17(Suppl 1):S58-S64.
  • Pellock JM, Glauser TA, Bebin EM, et al. Pharmacokinetic study of levetiracetam in children. Epilepsia. 2001;42:1574-1579.[CrossRef][Medline] [Order article via Infotrieve]
  • Leppik I, Morrell M, Godfroid P, Arrigo C. Seizure-free days observed in randomized placebo-controlled add-on trials with levetiracetam in partial epilepsy. Epilepsia. 2003;44:1350-1352.[Medline] [Order article via Infotrieve]
  • Gram L. Oxcarbazepine. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippencott-Raven; 1998;1541-1546.
  • Beydoun A, Kutluay E. Oxcarbazepine. Exper Opin Pharmacother. 2002;3:59-71.[CrossRef]
  • Friis ML, Kristensen O, Boas J, et al. Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment. Acta Neurol Scand. 1993;87:224-227.[Medline] [Order article via Infotrieve]
  • Schachter SC. Tiagabine. Epilepsia. 1999;40(Suppl 5):S17-S22.
  • Abbott Laboratories. Gabitril package insert. North Chicago, IL: Abbott Laboratories; 1999.
  • Samara EE, Gustavson LE, Shourbagy TE, Locke C, Granneman GR, Sommerville KW. Population analysis of the pharmacokinetics of tiagabine in patients with epilepsy. Epilepsia. 1998;39:868-873.[CrossRef][Medline] [Order article via Infotrieve]
  • Pellock JM. Tiagabine (Gabitril) experience in children. Epilepsia. 2001;42(Suppl 3):49-51.
  • Sommerville KW. Tiagabine. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippencott-Raven; 1998:1645-1653.
  • Wang PWS, Ketter TA. Pharmacokinetics of mood stabilizers and new anticonvulsants. Psychopharmacol Bull. 2002;36:44-66.[Medline] [Order article via Infotrieve]
  • Williams J, Bialer M, Johannessen SI, et al. Interlaboratory variability in the quantification of new generation antiepileptic drugs based on external quality assessment data. Epilepsia. 2003;44:40-45.[Medline] [Order article via Infotrieve]
  • Ortho-McNeil Pharmaceutical. Topamax approved labeling text dated 6/29/05. Raritan, NJ: Ortho-McNeil Pharmaceutical; Retrieved October 10, 2005, from www.fda.gov/cder/foi/label/2005/020505s018lbl.pdf.
  • Glauser TA. Topiramate. Epilepsia. 1999;40(Suppl 5):S71-S80.
  • Garnett WR. Clinical pharmacology of topiramate: a review. Epilepsia. 2000;41(Suppl 1):S61-S65.[CrossRef]
  • Christensen J, Højskov CS, Dam M, Poulsen JH. Plasma concentration of topiramate correlates with cerebrospinal fluid concentration. Ther Drug Monit. 2001;23:529-535.[Medline] [Order article via Infotrieve]
  • Rosenfeld WE, Doose DR, Walker SA, Baldassarre JS, Reife RA. A study of topiramate pharmacokinetics and tolerability in children with epilepsy. Pediatr Neurol. 1999;20:339-344.[CrossRef][Medline] [Order article via Infotrieve]
  • Glauser TA, Miles MV, Tang P, Clark P, McGee K, Doose DR. Topiramate pharmacokinetics in infants. Epilepsia. 1999;40: 788-791.[CrossRef][Medline] [Order article via Infotrieve]
  • Sachdeo RC, Sachdeo SK, Levey RH, et al. Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Epilepsia. 2002;43:691-696.[CrossRef][Medline] [Order article via Infotrieve]
  • Doose DR, Brodie MJ, Wilson EA, et al. Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients. Epilepsia. 2003;44:917-922.[CrossRef][Medline] [Order article via Infotrieve]
  • May TW, Rambeck B, Jürgens U. Serum concentrations of topiramate in patients with epilepsy: influence of dose, age and comedication. Ther Drug Monit. 2002;24:366-374.[CrossRef][Medline] [Order article via Infotrieve]
  • Seino M, Ito T. Zonisamide. In: Engel J Jr, Pedley TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippencott-Raven; 1998;1621-1622.
  • Willmore LJ. Clinical pharmacology of new antiepileptic drugs. Neurology. 2000;55(Suppl 3):S17-S24.
  • Leppik IE. Zonisamide. Epilepsia. 1999;40(Suppl 5):S23-S29.
  • Mimaki T. Clinical pharmacology and therapeutic drug monitoring of zonisamide. Ther Drug Monit. 1998;20:593-597.[CrossRef][Medline] [Order article via Infotrieve]
  • Elan Biopharmaceuticals. Zonegran package insert. San Diego, CA: Elan Biopharmaceuticals; 2003.
  • Gidal BE, Garnett WR Graves N. Epilepsy. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York: McGraw-Hill; 2002:1031-1059.

Journal of Pharmacy Practice, Vol. 18, No. 6, 444-460 (2005)
DOI: 10.1177/0897190005282733
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