Skip to main content
Log in

Pharmacokinetic Interactions of the New Antiepileptic Drugs

  • Review Article
  • Drug Interactions
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Therapy with traditional antiepileptic drugs is associated with a wide range of pharmacokinetic drug-drug interactions. In particular, enzyme induction, enzyme inhibition and displacement from protein binding may result in important changes in serum concentrations of antiepileptics. Relevant interactions have also been described for some new antiepileptics.

Felbamate increases serum concentrations of phenytoin, phenobarbital and valproic acid (sodium valproate). On the other hand, it reduces concentrations of carbamazepine and increases concentrations of its metabolite carbamazepine-10,11-epoxide. Concentrations of felbamate itself are reduced by phenytoin and carbamazepine. Concentrations of lamotrigine are considerably increased by valproic acid and decreased by phenytoin, carbamazepine and phenobarbital (phenobarbitone). Vigabatrin reduces serum concentrations of phenytoin by approximately 20%.

On the other hand, some new antiepileptics have the important advantage of not interfering with the metabolism of other antiepileptics; this is the case for gabapentin, lamotrigine and oxcarbazepine. Furthermore, the pharmacokinetics of gabapentin, oxcarbazepine and vigabatrin are independent of concomitant drugs. These aspects are especially important as, until now, new antiepileptics have been most often utilised as add-on therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Patsalos PN, Duncan JS. Antiepileptic drugs: a review of clinically significant drug interactions. Drug Saf 1993; 9: 156–84

    PubMed  CAS  Google Scholar 

  2. Theodore WH, Jensen PK, Kwan RMR. Felbamate: clinical use. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. New York: Raven Press, 1995: 817–22

    Google Scholar 

  3. Leppik IE. Felbamate. Epilepsia 1995; 36 Suppl. 2: 66–72

    Google Scholar 

  4. Perucca E. The clinical pharmacology of the new antiepileptic drugs. Pharmacol Res 1993; 28: 89–106

    PubMed  CAS  Google Scholar 

  5. Wilensky AJ, Friel PN, Ojemann LM, et al. Pharmacokinetics of W-554 (ADD 03055) in epileptic patients. Epilepsia 1985; 26: 602–6

    PubMed  CAS  Google Scholar 

  6. Fuerst RH, Graves NM, Leppik IE, et al. Felbamate increases phenytoin but decreases carbamazepine concentrations. Epilepsia 1988; 29: 488–91

    PubMed  CAS  Google Scholar 

  7. Graves NM, Holmes GB, Fuerst RH, et al. Effect of felbamate on phenytoin and carbamazepine serum concentrations. Epilepsia 1989; 30: 225–9

    PubMed  CAS  Google Scholar 

  8. Theodore WH, Raubertas RF, Porter RJ, et al. Felbamate: a clinical trial for complex partial seizures. Epilepsia 1991; 32: 392–7

    PubMed  CAS  Google Scholar 

  9. Albani F, Theodore WH, Washington P, et al. Effect of felbamate on plasma levels of carbamazepine and its metabolites. Epilepsia 1991; 32: 130–2

    PubMed  CAS  Google Scholar 

  10. Wagner ML, Remmel RP, Graves NM, et al. Effect of felbamate on carbamazepine and its major metabolites. Clin Pharmacol Ther 1993; 53: 536–43

    PubMed  CAS  Google Scholar 

  11. Reidenberg P, Glue P, Banfield CR, et al. Effects of felbamate on the pharmacokinetics of phenobarbital. Clin Pharmacol Ther 1995; 58: 279–87

    PubMed  CAS  Google Scholar 

  12. Wagner ML, Graves NM, Leppik IE, et al. The effect of felbamate on valproic acid disposition. Clin Pharmacol Ther 1994; 56: 494–502

    PubMed  CAS  Google Scholar 

  13. Hooper WD, Franklin ME, Glue P, et al. Effect of felbamate on valproic acid disposition in healthy volunteers: inhibition of β-oxidation. Epilepsia 1996; 37: 91–7

    PubMed  CAS  Google Scholar 

  14. Bernus I, Dickinson RG, Hooper WD, et al. Effect of felbamate on the plasma protein binding of valproate. Clin Drug Invest 1995; 10: 288–95

    CAS  Google Scholar 

  15. Reidenberg P, Glue P, Banfield C, et al. Pharmacokinetic interaction studies between felbamate and vigabatrin. Br J Clin Pharmacol 1995; 40: 157–60

    PubMed  CAS  Google Scholar 

  16. Hulsman JARJ, Rentmeester TW, Banfield CR, et al. Effects of felbamate on the pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbazepine. Clin Pharmacol Ther 1995; 58: 383–9

    PubMed  CAS  Google Scholar 

  17. Saano V, Glue P, Banfield CR, et al. Effects of felbamate on the pharmacokinetics of low-dose combination oral contraceptive. Clin Pharmacol Ther 1995; 58: 523–31

    PubMed  CAS  Google Scholar 

  18. Wagner ML, Graves NM, Marienau K, et al. Discontinuation of phenytoin and carbamazepine in patients receiving felbamate. Epilepsia 1991; 32: 398–406

    PubMed  CAS  Google Scholar 

  19. Wagner ML, Leppik IE, Graves NM, et al. Felbamate serum concentrations: effect of valproate, carbamazepine, phenytoin and phenobarbital [abstract]. Epilepsia 1990; 31: 642

    Google Scholar 

  20. Brodie MJ. Felbamate: a new antiepileptic drug. Lancet 1993; 341: 1445–6

    PubMed  CAS  Google Scholar 

  21. Burdette DE, Sackellares JC. Felbamate pharmacology and use in epilepsy. Clin Neuropharmacol 1994; 17: 389–402

    PubMed  CAS  Google Scholar 

  22. Graves NM. Felbamate. Ann Pharmacother 1993; 27: 1073–81

    PubMed  CAS  Google Scholar 

  23. Palmer KJ, McTavish D. Felbamate: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in epilepsy. Drugs 1993; 45: 1041–65

    PubMed  CAS  Google Scholar 

  24. Goa KL, Sorkin EM. Gabapentin: a review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993; 46: 409–27

    PubMed  CAS  Google Scholar 

  25. Hooper WD, Kavanagh MC, Herkes GK, et al. Lack of a pharmacokinetic interaction between phenobarbitone and gabapentin. Br J Clin Pharmacol 1991; 31: 171–4

    PubMed  CAS  Google Scholar 

  26. Crawford P, Ghadiali E, Lane R, et al. Gabapentin as an antiepileptic drug in man. J Neurol Neurosurg Psychiatry 1987; 50: 682–6

    PubMed  CAS  Google Scholar 

  27. Radulovic LL, Wilder BJ, Leppik IE, et al. Lack of interaction of gabapentin with carbamazepine or valproate. Epilepsia 1994; 35: 155–61

    PubMed  CAS  Google Scholar 

  28. US Gabapentin Study Group. The long-term safety and efficacy of gabapentin (Neurontin®) as add-on therapy in drug-resistant partial epilepsy. Epilepsy Res 1994; 18: 67–73

    Google Scholar 

  29. Tyndel F. Interaction of gabapentin with other antiepileptics. Lancet 1994; 343: 1363–4

    PubMed  CAS  Google Scholar 

  30. Eldon MA, Underwood BA, Randinitis EJ, et al. Lack of effect of gabapentin on the pharmacokinetics of a norethindrone acetate/ethinyl estradiol-containing oral contraceptive [abstract]. Neurology 1993; 43: A307–A8

    Google Scholar 

  31. McLean MJ. Clinical pharmacokinetics of gabapentin. Neurology 1994; 44 Suppl. 5: 17–22

    Google Scholar 

  32. Ramsay RE. Clinical efficacy and safety of gabapentin. Neurology 1994; 44 Suppl. 5: 23–30

    Google Scholar 

  33. Busch JA, Radulovic LL, Bockbrader HN, et al. Effect of maalox TC on single-dose pharmacokinetics of gabapentin capsules in healthy subjects [abstract]. Pharm Res 1992; 9 Suppl. 2: S315

    Google Scholar 

  34. Goa KL, Ross SR, Chrisp P. Lamotrigine: a review of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1993; 46: 152–76

    PubMed  CAS  Google Scholar 

  35. Timmings PL, Richens A. Lamotrigine in primary generalised epilepsy. Lancet 1992; 339: 1300–1

    PubMed  CAS  Google Scholar 

  36. Ferrie CD, Robinson RO, Knott C, et al. Lamotrigine as an add-on drug in typical absence seizures. Acta Neurol Scand 1995; 91: 200–2

    PubMed  CAS  Google Scholar 

  37. Jawad S, Yuen WC, Peck AW, et al. Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy. Epilepsy Res 1987; 1: 194–201

    PubMed  CAS  Google Scholar 

  38. Loiseau P, Yuen AWC, Duche B, et al. A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures. Epilepsy Res 1990; 7: 136–45

    PubMed  CAS  Google Scholar 

  39. Sander JWAS, Patsalos PN, Oxley JR, et al. A randomized double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy. Epilepsy Res 1990; 6: 221–6

    PubMed  CAS  Google Scholar 

  40. Jawad S, Richens A, Goodwin G, et al. Controlled trial of lamotrigine (Lamictal®) for refractory partial seizures. Epilepsia 1989; 30: 356–63

    PubMed  CAS  Google Scholar 

  41. Schapel GJ, Beran RG, Vajda FJE, et al. Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures. J Neurol Neurosurg Psychiatry 1993; 56: 448–53

    PubMed  CAS  Google Scholar 

  42. Posner J, Webster H, Yuen WC. Investigation on the ability of lamotrigine, a novel antiepileptic drug, to induce mixed function oxygenase enzymes. Br J Clin Pharmacol 1991; 32: 658

    Google Scholar 

  43. Warner T, Patsalos PN, Prevett M, et al. Lamotrigine-induced carbamazepine toxicity: an interaction with carbamazepine-10,11-epoxide. Epilepsy Res 1992; 11: 147–50

    PubMed  CAS  Google Scholar 

  44. Wolf P. Lamotrigine: preliminary clinical observations on pharmacokinetics and interactions with traditional antiepileptic drugs. J Epilepsy 1992; 5: 73–9

    Google Scholar 

  45. Pisani F, Xiao B, Fazio A, et al. Single dose pharmacokinetics of carbamazepine-10,11-epoxide in patients on lamotrigine monotherapy. Epilepsy Res 1994; 19: 245–8

    PubMed  CAS  Google Scholar 

  46. Buchanan N. Lamotrigine: clinical experience in 93 patients with epilepsy. Acta Neurol Scand 1995; 92: 28–32

    PubMed  CAS  Google Scholar 

  47. Holdich T, Whiteman P, Orme M, et al. Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill [abstract]. Epilepsia 1991; 32 Suppl. 1: 96

    Google Scholar 

  48. Binnie CD, van Emde Boas W, Kasteleijn-Nolste-Trenite DGA, et al. Acute effects of lamotrigine (BW430C) in persons with epilepsy. Epilepsia 1986; 27: 248–54

    PubMed  CAS  Google Scholar 

  49. Yuen AWC, Land G, Weatherley BC, et al. Sodium valproate acutely inhibits lamotrigine metabolism. Br J Clin Pharmacol 1992; 33: 511–3

    PubMed  CAS  Google Scholar 

  50. May TW, Rambeck B, Jürgens U. Serum concentrations of lamotrigine in epileptic patients: the influence of dose and comedication. Ther Drug Monit 1996 Autumn; 18. In press

  51. Depot M, Powell JR, Messenheimer JA, et al. Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. Clin Pharmacol Ther 1990; 48: 346–55

    PubMed  CAS  Google Scholar 

  52. Panayiotopoulos CP, Ferrie CD, Knott C, et al. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 445

    PubMed  CAS  Google Scholar 

  53. Ferrie CD, Panayiotopoulos CP. Therapeutic interaction of lamotrigine and sodium valproate in intractable myoclonic epilepsy. Seizure 1994; 3: 157–9

    PubMed  CAS  Google Scholar 

  54. Pisani F, Di Perri R, Perucca E, et al. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 1224

    PubMed  CAS  Google Scholar 

  55. Pisani F, Oteri G, Russo M, et al. Effects of lamotrigine-valproate comedication on seizure frequency and upper limb tremor: a pharmacodynamic interaction? [abstract]. Epilepsia 1995; 36 Suppl. 3: S264

    Google Scholar 

  56. Reutens DC, Duncan JS, Patsalos PN. Disabling tremor after lamotrigine with sodium valproate. Lancet 1993; 342: 185–6

    PubMed  CAS  Google Scholar 

  57. Brodie MJ. Lamotrigine. Lancet 1992; 339: 1397–400

    PubMed  CAS  Google Scholar 

  58. Rambeck B, Wolf P. Lamotrigine clinical pharmacokinetics. Clin Pharmacokinet 1993; 25: 433–43

    PubMed  CAS  Google Scholar 

  59. Messenheimer JA. Lamotrigine. Clin Neuropharmacol 1994; 17: 548–59

    Google Scholar 

  60. Messenheimer JA. Lamotrigine. Epilepsia 1995; 36 Suppl. 2: 87–94

    Google Scholar 

  61. Burstein AH. Lamotrigine. Pharmacotherapy 1995; 15: 129–43

    PubMed  CAS  Google Scholar 

  62. Grant SM, Faulds D. Oxcarbazepine: a review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders. Drugs 1992; 43: 873–88

    PubMed  CAS  Google Scholar 

  63. McKee PJW, Blacklaw J, Forrest G, et al. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Br J Clin Pharmacol 1994; 37: 27–32

    PubMed  CAS  Google Scholar 

  64. Battino D, Croci D, Granata T, et al. Changes in unbound and total valproic acid concentrations after replacement of carbamazepine with oxcarbazepine. Ther Drug Monit 1992; 14: 376–9

    PubMed  CAS  Google Scholar 

  65. Houtkooper MA, Lammertsma A, Meyer JWA, et al. Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine? Epilepsia 1987; 28: 693–8

    PubMed  CAS  Google Scholar 

  66. Larkin JG, McKee PJW, Forrest G, et al. Lack of enzyme induction with oxcarbazepine (600mg daily) in healthy subjects. Br J Clin Pharmacol 1991; 31: 65–71

    PubMed  CAS  Google Scholar 

  67. Krämer G, Tettenborn B, Klosterskov Jensen P, et al. Oxcarbazepine does not affect the anticoagulant activity of warfarin. Epilepsia 1992; 33: 1145–8

    PubMed  Google Scholar 

  68. Lloyd P, Flesch G, Dieterle W. Clinical pharmacology and pharmacokinetics of oxcarbazepine. Epilepsia 1994; 35 Suppl. 3: 10–3

    Google Scholar 

  69. Klosterskov Jensen P, Saano V, Haring P, et al. Possible interaction between oxcarbazepine and an oral contraceptive. Epilepsia 1992; 33: 1149–52

    PubMed  CAS  Google Scholar 

  70. Zaccara G, Gangemi PF, Bendoni L, et al. Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine. Ther Drug Monit 1993; 15: 39–42

    PubMed  CAS  Google Scholar 

  71. Patsalos PN, Zakrzewska JM, Elyas AA. Dose dependent enzyme induction by oxcarbazepine. Eur J Clin Pharmacol 1990; 39: 187–8

    PubMed  CAS  Google Scholar 

  72. Tartara A, Galimberti CA, Manni R, et al. The pharmacokinetics of oxcarbazepine and its active metabolite 10-hydroxy-carbazepine in healthy subjects and in epileptic patients treated with phenobarbitone or valproic acid. Br J Clin Pharmacol 1993; 36; 366–8

    PubMed  CAS  Google Scholar 

  73. Arnoldussen W, Hulsman J, Rentmeester T. Interaction between oxcarbazepine and phenytoin [abstract]. Epilepsia 1993; 34 Suppl. 6: 37

    Google Scholar 

  74. Kumps A, Wuth C. Oxcarbazepine disposition: preliminary observations in patients. Biopharm Drug Dispos 1990; 11: 365–70

    PubMed  CAS  Google Scholar 

  75. Keränen T, Jolkkonen J, Jensen PK, et al. Absence of interaction between oxcarbazepine and erythromycin. Acta Neurol Scand 1992; 86: 120–3

    PubMed  Google Scholar 

  76. Keränen T, Jolkkonen J, Klosterskov-Jensen P, et al. Oxcarbazepine does not interact with cimetidine in healthy volunteers. Acta Neurol Scand 1992; 85: 239–42

    PubMed  Google Scholar 

  77. Mogensen PH, Jorgensen L, Boas J, et al. Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites. Acta Neurol Scand 1992; 85: 14–7

    PubMed  CAS  Google Scholar 

  78. Pisani F, Fazio A, Oteri G, et al. Effects of the antidepressant drug viloxazine on oxcarbazepine and its hydroxylated metabolites in patients with epilepsy. Acta Neurol Scand 1994; 90: 130–2

    PubMed  CAS  Google Scholar 

  79. Krämer G, Tettenborn B, Flesch G. Oxcarbazepine-verapamil drug interaction in healthy volunteers [abstract]. Epilepsia 1991; 32 Suppl. 1: 70–1

    Google Scholar 

  80. Faigle JW, Menge GP. Pharmacokinetic and metabolic features of oxcarbazepine and their clinical significance: comparison with carbamazepine. Int Clin Psychopharmacol 1990; 5: 73–82

    Google Scholar 

  81. Baruzzi A, Albani F, Riva R. Oxcarbazepine: pharmacokinetic interactions and their clinical relevance. Epilepsia 1994; 35 Suppl. 3: 14–9

    Google Scholar 

  82. Grant SM, Heel RC. Vigabatrin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs 1991; 41: 889–926

    PubMed  CAS  Google Scholar 

  83. Rimmer EM, Richens A. Double-blind study of γ-vinyl GABA in patients with refractory epilepsy. Lancet 1984; 1: 189–90

    PubMed  CAS  Google Scholar 

  84. Browne TR, Mattson RH, Penry JK, et al. Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow-up. Neurology 1987; 37: 184–9

    PubMed  CAS  Google Scholar 

  85. Browne TR, Mattson RH, Penry JK, et al. A multicentre study of vigabatrin for drug-resistant epilepsy. Br J Clin Pharmacol 1989; 27 Suppl. 1: 95–100

    Google Scholar 

  86. Dalla Bernardina B, Fontana E, Vigevano F, et al. Efficacy and tolerability of vigabatrin in children with refractory partial seizures: a single-blind dose-increasing study. Epilepsia 1995; 36: 687–91

    PubMed  CAS  Google Scholar 

  87. Rimmer EM, Richens A. Interaction between vigabatrin and phenytoin. Br J Clin Pharmacol 1989; 27: S27–S33

    Google Scholar 

  88. Gatti G, Bartoli A, Marchiselli R, et al. Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability. Br J Clin Pharmacol 1993; 36: 603–6

    PubMed  CAS  Google Scholar 

  89. Armijo JA, Arteaga R, Valdizán EM, et al. Coadministration of vigabatrin and valproate in children with refractory epilepsy. Clin Neuropharmacol 1992; 15: 459–69

    PubMed  CAS  Google Scholar 

  90. Gram L, Klosterskov P, Dam M. γ-Vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy. Ann Neurol 1985; 17: 262–6

    PubMed  CAS  Google Scholar 

  91. Loiseau P, Hardenberg JP, Pestre M, et al. Double-blind, placebo-controlled study of vigabatrin (Gamma-Vinyl GABA) in drug-resistant epilepsy. Epilepsia 1986; 27: 115–20

    PubMed  CAS  Google Scholar 

  92. Luna D, Dulac O, Pajot N, et al. Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study. Epilepsia 1989; 30: 430–7

    PubMed  CAS  Google Scholar 

  93. Matilainen R, Pitkänen A, Ruutiainen T, et al. Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study. Neurology 1988; 38: 743–7

    PubMed  CAS  Google Scholar 

  94. Cocito L, Maffini M, Perfumo P, et al. Vigabatrin in complex partial seizures: a long-term study. Epilepsy Res 1989; 3: 160–6

    PubMed  CAS  Google Scholar 

  95. Szylleyko OJ, Hoke JF, Eller MG, et al. A definitive study evaluating the pharmacokinetic of vigabatrin in patients with epilepsy [abstract]. Epilepsia 1993; 34 Suppl. 6: 41–2

    Google Scholar 

  96. Ben-Menachem E. Vigabatrin. Epilepsia 1995; 36 Suppl. 2: 95–104

    Google Scholar 

  97. Rey E, Pons G, Olive G. Vigabatrin: clinical pharmacokinetics. Clin Pharmacokinet 1992; 23: 267–78

    PubMed  CAS  Google Scholar 

  98. Richens A. Pharmacology and clinical pharmacology of vigabatrin. J Child Neurol 1991; 6 Suppl. 2: S7–S10

    Google Scholar 

  99. Richens A. Pharmacokinetic and pharmacodynamic drug interactions during treatment with vigabatrin. Acta Neurol Scand 1995; Suppl. 162: 43–6

    Google Scholar 

  100. Sabers A, Gram L. Pharmacology of vigabatrin. Pharmacol Toxicol 1992; 70: 237–43

    PubMed  CAS  Google Scholar 

  101. Peters DH, Sorkin EM. Zonisamide: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs 1993; 45: 760–87

    PubMed  CAS  Google Scholar 

  102. Sackellares JC, Donofrio PD, Wagner JG, et al. Pilot study of zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in patients with refractory partial seizures. Epilepsia 1985; 26: 206–11

    PubMed  CAS  Google Scholar 

  103. Minami T, Ieiri I, Ohtsubo K, et al. Influence of additional therapy with zonisamide (excegran) on protein binding and metabolism of carbamazepine. Epilepsia 1994; 35: 1023–5

    PubMed  CAS  Google Scholar 

  104. Browne TR, Szabo GK, Kres J, et al. Drug interactions of zonisamide (DI-912) with phenytoin and carbamazepine [abstract]. J Clin Pharmacol 1986; 26: 555

    Google Scholar 

  105. Schmidt D, Jacob R, Loiseau P, et al. Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. Epilepsy Res 1993; 15: 67–73

    PubMed  CAS  Google Scholar 

  106. Tasaki K, Minami T, Ieiri I, et al. Drug interactions of zonisamide with phenytoin and sodium valproate: serum concentrations and protein binding. Brain Dev 1995; 17: 182–5

    PubMed  CAS  Google Scholar 

  107. Ojemann LM, Shastri RA, Wilensky AJ, et al. Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy. Ther Drug Monit 1986; 8: 293–6

    PubMed  CAS  Google Scholar 

  108. Kimura M, Tanaka N, Kimura Y, et al. Factors influencing serum concentration of zonisamide in epileptic patients. Chem Pharm Bull 1992; 40: 193–5

    PubMed  CAS  Google Scholar 

  109. Stables JP, Bialer M, Johannessen SI, et al. Progress report on new antiepileptic drugs: a summary of the Second Eilat Conference. Epilepsy Res 1995; 22: 235–46

    PubMed  CAS  Google Scholar 

  110. Britton JW, So EL. New antiepileptic drugs: prospects for the future. J Epilepsy 1995; 8: 267–81

    Google Scholar 

  111. Walker MC, Patsalos PN. Clinical pharmacokinetics of new antiepileptic drugs. Pharmacol Ther 1995; 67: 351–84

    PubMed  CAS  Google Scholar 

  112. Gustavson LE, Mengel HB. Pharmacokinetics of tiagabine, a γ-aminobutyric acid-uptake inhibitor, in healthy subjects after single and multiple doses. Epilepsia 1995; 36: 605–11

    PubMed  CAS  Google Scholar 

  113. Richens A, Chadwick DW, Duncan JS, et al. Adjunctive treatment of partial seizures with tiagabine: a placebo-controlled trial. Epilepsy Res 1995; 21: 37–42

    PubMed  CAS  Google Scholar 

  114. Brodie MJ. Tiagabine pharmacology in profile. Epilepsia 1995; 36 Suppl. 6: S7–S9

    PubMed  CAS  Google Scholar 

  115. So EL, Wolff D, Graves NM, et al. Pharmacokinetics of tiagabine as add-on therapy in patients taking enzyme-inducing antiepilepsy drugs. Epilepsy Res 1995; 22: 221–6

    PubMed  CAS  Google Scholar 

  116. Patsalos PN, Duncan JS. New antiepileptic drugs: a review of their current status and clinical potential. CNS Drugs 1994; 2: 40–77

    Google Scholar 

  117. Bebin M, Bleck TP. New anticonvulsant drugs: focus on flunarizine, fosphenytoin, midazolam and stiripentol. Drugs 1994; 48: 153–71

    PubMed  CAS  Google Scholar 

  118. Leach JP, Brodie MJ. New antiepileptic drugs: an explosion of activity. Seizure 1995; 4: 5–17

    PubMed  CAS  Google Scholar 

  119. Leppik IE, Dreifuss FE, Pledger GW, et al. Felbamate for partial seizures: results of a controlled clinical trial. Neurology 1991; 41: 1785–9

    PubMed  CAS  Google Scholar 

  120. Morris JC, Dodson WE, Hatlelid JM, et al. Phenytoin and carbamazepine, alone and in combination: anticonvulsant and neurotoxic effects. Neurology 1987; 37: 1111–8

    PubMed  CAS  Google Scholar 

  121. Porter RJ. How to use antiepileptic drugs. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. New York: Raven Press, 1995: 137–48

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rambeck, B., Specht, U. & Wolf, P. Pharmacokinetic Interactions of the New Antiepileptic Drugs. Clin-Pharmacokinet 31, 309–324 (1996). https://doi.org/10.2165/00003088-199631040-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199631040-00006

Keywords

Navigation