European Journal of Clinical Pharmacology

, Volume 61, Issue 12, pp 863–872 | Cite as

Alteration of thyroid hormone homeostasis by antiepileptic drugs in humans: involvement of glucuronosyltransferase induction

  • M. Strolin Benedetti
  • R. Whomsley
  • E. Baltes
  • F. Tonner
Review Article



The aim of this review article is to analyse which antiepileptic drugs (AEDs) alter thyroid hormone homeostasis in humans and when this can be explained, at least partially, by the induction of the glucuronoconjugation pathways.


Electronic databases were searched which have provided more than 300 articles. These have been integrated with fundamental books and personal information by experts in the different areas examined.


Alteration of thyroid hormone homeostasis by phenobarbital/primidone, phenytoin, and carbamazepine clearly occurs in humans. However, it is not associated with thyroid-stimulating hormone (TSH) increase and the clinical significance of altered serum concentrations of thyroid hormones by these antiepileptic drugs has remained unclear. The published information on the effect of the other antiepileptic drugs examined in this review article on thyroid hormones is lacking (felbamate, pregabalin, zonisamide) or limited. Oxcarbazepine appears to have some effects. Topiramate would need further investigations as well as gabapentin. Levetiracetam, tiagabine, vigabatrine, and lamotrigine do not alter at all, or only minimally, thyroid hormone homeostasis.


Concerning the antiepileptic drugs which alter thyroid hormone homeostasis, it is highly probable that the mechanism of induction of uridine diphosphate glucuronosyltransferases (UGT) is involved, at least partially, in such an alteration. However, it is not possible to estimate the relative contribution of the UGT induction by these drugs on the total alteration observed in thyroid hormone levels, as other mechanisms not investigated, or not examined in the present article, could contribute.


Antiepileptic drugs Glucuronosyltransferases Thyroid hormones 


  1. 1.
    Hennemann G, Visser TJ (1997) Thyroid hormone synthesis, plasma membrane transport and metabolism. In: Handbook of Experimental Pharmacology. Pharmacotherapeutics of the thyroid gland, vol 128. Springer, Berlin Heidelburg New York, pp 75–117Google Scholar
  2. 2.
    Engler D, Burger AG (1984) The deiodination of the iodothyronines and of their derivatives in man. Endocrin Rev 5:151Google Scholar
  3. 3.
    Curran PG, DeGroot LJ (1991) The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocrin Rev 12:135–150Google Scholar
  4. 4.
    Visser TJ, Kaptein E, Glatt H, Bartsch I, Hagen M, Coughtrie MWH (1998) Characterization of thyroid hormone sulfotransferases. Chem Biol Interact 109:279–291CrossRefPubMedGoogle Scholar
  5. 5.
    Kohrle J, Hesch RD, Leonard JL (1991) Intracellular pathways of iodothyronine metabolism. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s The thyroid: a Fundamental and Clinical Text. Lippincott, New York, pp 144–189Google Scholar
  6. 6.
    Visser TJ (1994) Role of sulfation in thyroid hormone metabolism. Chem Biol Interact 92:293–303CrossRefPubMedGoogle Scholar
  7. 7.
    Findlay KAB, Kaptein E, Visser TJ, Burchell B (2000) Characterization of the uridine diphosphate-glucuronosyltransferase-catalyzing thyroid hormone glucuronidation in man. J Clin Endocr Metab 85:2879–2883CrossRefPubMedGoogle Scholar
  8. 8.
    Li AP, Hartman NR, Lu C, Collins JM, Strong JM (1999) Effects of cytochrome P450 inducers on 17α-ethinyloestrradiol (EE2) conjugation by primary human hepatocytes. Br J Clin Pharmacol 48:733–742CrossRefPubMedGoogle Scholar
  9. 9.
    Gregory LG, Cameron GA, Harrison A, Hawksworth GM (1999) Induction of thyroid hormone metabolism by dexamethasone and triiodothyronine in hepatocytes cultured as spheroids. Human Exper Toxicol 8:523Google Scholar
  10. 10.
    Hood A, Klaassen CD (2000) Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues. Toxicol Appl Pharmacol 163:240–248CrossRefPubMedGoogle Scholar
  11. 11.
    Gregory LG, Cameron GA, Smith DA, Harrison A, Hawksworth GM (2000) Induction of hepatic deiodination: role in nongenotoxic carcinogenesis of the thyroid. Toxicol Letters 116 (S1):109 (abstr 396)Google Scholar
  12. 12.
    Gregory LG, Cameron GA, Smith DA, Harrison A, Hawksworth GM (2000) Regulation of deiodinase activity by cellular redox status. Drug Metab Rev 52 (S1):58 (abstr 115)Google Scholar
  13. 13.
    Hawksworth GM, Cameron GA, Smith DA, Harrison A, Gregory LG (2001) Redox status affects induction of hepatic deiodinases. In: Proceedings IXth International Congress of Toxicology, Australia, July, p 127 (abstr P2E21)Google Scholar
  14. 14.
    Gregory LG, Cameron GA, Harrison A, Smith DA, Hawksworth GM (1999) Induction of a novel hepatic deiodinase. In: ISSX Proceedings, vol. 14, 7th European ISSX Meeting, Budapest, August 1999, p 24 (abstr 47)Google Scholar
  15. 15.
    Cavalieri RR, Sung LC, Becker CE (1973) Effects of Phenobarbital on thyroxine and triiodothyronine kinetics in Grave’s disease. J Clin Endocrinol Metab 37:308PubMedGoogle Scholar
  16. 16.
    Rootwelt K, Ganes T, Johannessen SI (1978) Effects of carbamazepine, phenytoin and phenobarbitone on serum levels of thyroid hormones and thyrotropin in humans. Scand J Clin Lab Invest 38:731PubMedCrossRefGoogle Scholar
  17. 17.
    Yeo PPB, Bates D, Howe JG, Ratcliffe WA, Schardt CW, Heath A, Evered DC (1978) Anticonvulsant and thyroid function. Br Med J 1:1581PubMedGoogle Scholar
  18. 18.
    Ohnhaus EE, Burgi H, Burger A, Studer H (1981) The effect of antipyrine, Phenobarbital and rifampicin on thyroid hormone metabolism in man. Eur J Clin Invest 11:381PubMedGoogle Scholar
  19. 19.
    Liewendahl K, Majuri H., Helenius T (1978) Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs. Clin Endocrinol (Oxf) 8:185Google Scholar
  20. 20.
    Fischel H., Knopfle G (1978) Effects of anticonvulsant drugs on thyroid hormones in epileptic children. Epilepsia 19:w323CrossRefGoogle Scholar
  21. 21.
    Whomsley R, Strolin Benedetti M, Espié P, Chen C, Klaassen C, Oesch F, Baltes E (2004) Comparison of induction of glucuronidation of thyroid hormones and bilirubin in rat and human hepatocytes. In: Abstract book, MDO 2004, Mainz, 4–9 July, p 129 (P6-CH-21)Google Scholar
  22. 22.
    Chin W, Schussler GC (1968) Decreased serum free thyroxine concentration in patients treated with diphenylhydantoin. J Clin Endocrinol 28:181Google Scholar
  23. 23.
    Larsen PR, Atkinson AJ, Wellman HN, Goldsmith RE (1970) The effect of diphenylhydantoin on thyroxine metabolism in man. J Clin Invest 49:1266PubMedCrossRefGoogle Scholar
  24. 24.
    Siers-Baek NK, Moholm-Hansen J, Skovsted L (1972) Diphenylhydantoin and thyroid function. Isr J Med Sci 8:1868Google Scholar
  25. 25.
    Hanson JM, Skovsted L, Lauridsen UB, Kirkegaard C, Siersbaek-Nielsen K (1974) The effect of diphenylhydantoin on thyroid function. J Clin Endocrinol Metab 39:785PubMedGoogle Scholar
  26. 26.
    Stjernholm MR, Alsever RN, Rudolph MC (1975) Thyroid function tests in diphenylhydantoin-treated patients. Clin Chem 21:1388PubMedGoogle Scholar
  27. 27.
    Liewendahl K, Majuri H (1976) Thyroxine, triiodothyronine, and thyrotropin in serum during long-term diphenylhydantoin therapy. Scand J Clin Lab Invest 36:141PubMedCrossRefGoogle Scholar
  28. 28.
    Heyma P, Larkins RG, Perry-Keene D, Peter CT, Ross D, Sloman JG (1977) Thyroid hormone levels and protein binding in patients on long-term diphenylhydantoin treatment. Clin Endocrinol (Oxf) 6:369Google Scholar
  29. 29.
    Cavalieri RR, Gavin LA, Wallace A, Hammond ME, Cruse K (1979) Serum thyroxine, free T4, triiodothyronine, and reverse-T3 in diphenylhydantoin-treated patients. Metabolism 28:1161CrossRefPubMedGoogle Scholar
  30. 30.
    Liewendahl K, Helenius T, Majuri H., Ebeling P, Ahlfors UG (1980) Effects of anticonvulsant and antidepressant drugs on iodothyroxines in serum. Scand J Clin Lab Invest 40:767PubMedCrossRefGoogle Scholar
  31. 31.
    Surks MI, Ordene KW, Mann DN, Kumara-Siri MH (1983) Diphenylhydantoin inhibits the thyrotropin response to thyrotropin-releasing hormone in man and rat. J Clin Endocrinol Metab 56:940PubMedGoogle Scholar
  32. 32.
    Hüffner M, Knöpfle M (1976) Pharmacological influences of T4 to T3 conversion in rat liver. Clin Chim Acta 72:337–341CrossRefPubMedGoogle Scholar
  33. 33.
    Cullen MJ, Burger AG, Ingbar SH (1972) Effects of diphenylhydantoin on peripheral thyroid hormone economy and the conversion of T4 to T3. Isr J Med Sci 8:1868Google Scholar
  34. 34.
    Mann DN, Kumara-Siri MH, Surks MI (1983) Effect of 5,5′-diphenylhydantoin on the activities of hepatic cystosol malic enzyme and mitochondrial α-glycerophosphate dehydrogenase in athyreotic rats. Endocrinology 112:1732–1738PubMedGoogle Scholar
  35. 35.
    Smith PJ, Surks MI (1984) 5,5′-Diphenylhydantoin (Dilantin) decreases cytosol and specific nuclear 3,5,3′- triiodothyronine binding in rat anterior pituitary in viov and in cultured GC cells. Endocrinology 115:283–290PubMedCrossRefGoogle Scholar
  36. 36.
    Anderson GD (1998) A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother 32:554–563CrossRefPubMedGoogle Scholar
  37. 37.
    Mula M, Monaco F (2002) Antiepileptic-antipsychotic drug interactions: a critical review of the evidence. Clin Neuropharmacol 25:280–289CrossRefPubMedGoogle Scholar
  38. 38.
    Tanaka E (1999) Clinically significant pharmacokinetic drug interactions between antiepileptic drugs. J Clin Pharm Ther 24:87–92CrossRefPubMedGoogle Scholar
  39. 39.
    Kuhn-John G (2002) Influence of anticonvulsants on the metabolism and elimination of irinotecan, a North American brain tumor consortium preliminary report. Oncology 16:33–40Google Scholar
  40. 40.
    Riva R, Albani F, Contin M, Baruzzi A (1996) Pharmacokinetic interactions between antiepileptic drugs, clinical considerations. Clin Pharmacokin 31:470–493CrossRefGoogle Scholar
  41. 41.
    Bock KW, Bock-Hennig BS (1987) Differential induction of human liver UDP-glucuronosyltransferase activities by Phenobarbital-type inducers. Biochem Pharmacol 36:4136–4143CrossRefGoogle Scholar
  42. 42.
    Scott AK, Khir AS, Steele WH, Hawksworth GM, Petrie JC (1983) Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Br J Clin Pharmacol 16:441–444PubMedGoogle Scholar
  43. 43.
    Blackshear JL, Schultz AL, Napier JS, Stuart DD (1983) Thyroxine replacement in hypothyroid patients receiving phenytoin. Ann Internal Med 99:341–342Google Scholar
  44. 44.
    Franklyn JA, Sheppard MC, Ramsden DB (1984) Measurement of free thyroid hormones in patients on long-term phenytoin therapy. Eur J Clin Pharmacol 26:633–634CrossRefPubMedGoogle Scholar
  45. 45.
    Bentsen KD, Gram L, Veje A (1983) Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate. Acta Neurol Scand 67:235PubMedCrossRefGoogle Scholar
  46. 46.
    Vainionpää LK, Mikkonen K, Rättyä J, Knip M, Pakarinen AJ, Myllylä VV, Isojärvi JIT (2004) Thyroid function in girls with epilepsy with carbamazepine, oxcarbamazepine, or valproate monotherapy and after withdrawal of medication. Epilepsia 45:197–203CrossRefPubMedGoogle Scholar
  47. 47.
    Connell JM, Rapeport WG, Gordon S, Brodie MJ (1984) Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine. Eur J Clin Pharmacol 26:453–456CrossRefPubMedGoogle Scholar
  48. 48.
    Soars MG, Petullo DM, Eckstein JA, Kasper SC, Wrighton SA (2004) An assessment of UDP-glucuronosyltransferase induction using primary human hepatocytes. Drug Metab Dispos 32:140–148CrossRefPubMedGoogle Scholar
  49. 49.
    Spina E, Pisani F, Perruca E (1996) Clinically significant pharmacokinetic drug interactions with carbamazepine, an uptdate. Clin Pharmacokin 31:198–214Google Scholar
  50. 50.
    Yue Q, von Bahr C, Odar-Cederlöf I, Säwe J (1990) Glucuronidation of codeine and morphine in human liver and kidney microsomes: effects of inhibitors. Pharmacol Toxicol 66:221–226PubMedCrossRefGoogle Scholar
  51. 51.
    Spina E, Scordo MG (2004) Drug interactions in epilepsy. In: Shorvon S, Perucca E, Fish D, Dodson E (eds) The treatment of epilepsy, 2nd edn. Blackwell Science, Malden, Mass., pp 120–136Google Scholar
  52. 52.
    Antiepileptic drugs. In: Drug-drug interactions in the elderly with epilepsy: focus on antiepileptic, psychiatric, and cardiovascular drugs. Profiles in seizure management, Princeton Media associates, Millstone Twp. (NJ).
  53. 53.
    Yuen AWC (1995) Lamotrigine: interactions with other drugs. In: Levy RH, Mattson RH, Meldrum BS (eds) Antiepileptic drugs, 4th edn. Raven Press, New York, pp 883–887Google Scholar
  54. 54.
    Anderson GD, Gidal BE, Kantor E, Wilensky AJ (1994) Lorazepam-valproic acid interaction: studies in normal subjects and isolated perfused rat liver. Epilepsia 35:221–225PubMedCrossRefGoogle Scholar
  55. 55.
    Lertora JJ, Rege AB, Greenspan DL, Akula S (1994) Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 56:272–278PubMedCrossRefGoogle Scholar
  56. 56.
    Isojärvi JIT, Turkka J, Pakarinen AJ, Kotila M, Rättyä J, Myllylä VV (2001) Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia 42:930–934CrossRefPubMedGoogle Scholar
  57. 57.
    Gidal BE, Anderson GD, Spencer NW, Maly MM, Murty J, Pitterle ME, Collins DM, Davies LA (1996) Valproate-associated weight gain: potential relation to energy expenditure and metabolism in patients with epilepsy. J Epilepsy 9:234–241CrossRefGoogle Scholar
  58. 58.
    Richens A (1993) Clinical pharmacokinetics of gabapentin. In: Chadwick D (ed) New trends in epilepsy management: the role of gabapentin. Royal Society of Medicine Services International Congress and Symposium Series N° 198, Royal Society of Medicine Services, pp 41–46Google Scholar
  59. 59.
    Goa KL, Sorkin EM (1993) Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. Drugs 46:409–427PubMedCrossRefGoogle Scholar
  60. 60.
    Crawford P, Ghadiali E, Lane R, Blumhardt L, Chadwick D (1987) Gabapentin as an antiepileptic drug in man. J Neurol Neurosurg Psychiatry 50:682–686PubMedCrossRefGoogle Scholar
  61. 61.
    Radulovic LL, Wilder BJ, Leppik IE, Bockerbrader HN, Chang T, Posvar EL (1994) Lack of interaction of gabapentin with carbamazepine or valproate. Epilepsia 35:155–161PubMedCrossRefGoogle Scholar
  62. 62.
    US Gabapentin Study Group (1994) The long term safety and efficacy of gabapentin (Neurontin®) as add-on therapy in drug-resistant partial epilepsy. Epilepsy Res 18:67–73CrossRefGoogle Scholar
  63. 63.
    Burchel B (1999) Transformation reactions: glucuronidation. In : Woolf TF (ed) Handbook of drug metabolism. Drekker, New York, pp 153–173Google Scholar
  64. 64.
    Frye MA, Luckenbaugh D, Kimbrell TA, Constantino C, Grothe D, Corá-Locatelli G, Ketter TA (1999) Possible gabapentin-induced thyroiditis. Letter to the Editors. J Clin Psychopharmacol 19:94–95CrossRefPubMedGoogle Scholar
  65. 65.
    Lamotrigine (1999) In: Dollery C (ed) Therapeutic drugs, vol 2, 2nd edn. Churchill Livingstone, Edinburgh, pp L9–L13Google Scholar
  66. 66.
    Levy RH, Mather GG (1998) Metabolic enzymes and antiepileptic drug interactions. Antiepileptic Drug Dev Adv Neurol 76:49–55Google Scholar
  67. 67.
    Bourgeois BFD (1995) Important pharmacokinetic properties of antiepileptic drugs. Epilepsia 36:S1–S7PubMedCrossRefGoogle Scholar
  68. 68.
    Ramsay RE, Pellock JM, Garnett WR, Sanchez RM, Valakas AM, Wargin WA, Lai AA, Hubbell J, Chern WH, Allsup T, Otto V (1991) Pharmacokinetics and safety of lamotrigine (Lamictal) in patients with epilepsy. Epilepsy Res 10:191–200CrossRefPubMedGoogle Scholar
  69. 69.
    Garnett WR (1997) Lamotrigine: pharmacokinetics. J Child Neurol 12:S10–S15PubMedCrossRefGoogle Scholar
  70. 70.
    Richens A (1992) Pharmacokinetics of lamotrigine. In: Richens A (ed) Clinical update on lamotrigine: a novel antiepileptic agent. Wells Medical, pp 21–27Google Scholar
  71. 71.
    Yau MK, Adams MA, Wargin WA, Lai AA (1992) A single-dose and steady state pharmacokinetic study of lamotrigine in healthy male volunteers. In: Proceedings 3rd International Cleveland Clinic–Bethel Epilepsy Symposium on Antiepileptic Drug Pharmacology, June 16–19, ClevelandGoogle Scholar
  72. 72.
    GD Anderson Gidal BE, Levy RH, Yau MK, Wolf KG, Lai AA (1992) Effect of lamotrigine (LTG, Lamictal) on the pharmacokinetics and biotransformation of valproate. Epilepsia 33:82CrossRefGoogle Scholar
  73. 73.
    Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B, Ruus P, Engel J, Tukey RH, Kronbach T (1999) Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos 27:605–612PubMedGoogle Scholar
  74. 74.
    Magdalou J, Herber R, Bidault R, Siest G (1992) In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharmacol Exp Ther 260:1166–1173PubMedGoogle Scholar
  75. 75.
    Green MD, Te^hly TH (1998) Glucuronidation of amine substrates by purified and expressed UDP-glucuronosyltransferase proteins. Drug Metab Dispos 26:860–867PubMedGoogle Scholar
  76. 76.
    Goodwin GM, Bowden CL, Calabrese JR, Grunze H, Kasper S, White R, Greene P, Leadbetter R (2004) A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry 65:432–441PubMedCrossRefGoogle Scholar
  77. 77.
    Goodwin FK, Jamison KR (1990) Manic-depressive illness. Oxford University Press, New YorkGoogle Scholar
  78. 78.
    Strolin Benedetti M, Whomsley R, Nicolas JM, Young C, Baltes E (2003) Pharmacokinetics and metabolism of 14C-levetiracetam, a new antepileptic agent, in healthy volunteers. Eur J Clin Pharmacol 59:621–630CrossRefPubMedGoogle Scholar
  79. 79.
    Strolin Benedetti M (2000) Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fund Clin Pharmacol 14:301–319CrossRefGoogle Scholar
  80. 80.
    Shorvon S (2000) Oxcarbazepine: a review. Seizure 9:75–79CrossRefPubMedGoogle Scholar
  81. 81.
    Guenault N, Odou P, Robert H (2003) Increase in dihydroxycarbamazepine serum levels in patients co-medicated with oxcarbazepine and lamotrigine. Eur J Clin Pharmacol 59:781–782CrossRefPubMedGoogle Scholar
  82. 82.
    May TW, Rambeck B (1998) Influence of oxcarbazepine and methsuximide on LTG concentration. Epilepsia 39:25Google Scholar
  83. 83.
    May TW, Rambeck B, Jürgens U (1999) Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Ther Drug Monitor 21:175–181CrossRefGoogle Scholar
  84. 84.
    Isojärvi JIT, Juhani Airaksinen KE, Mustonen JN, Pakarinen AJ, Rautio A, Pelkonen O, Myllylä VV (1995) Thyroid and myocardial function after replacement of carbamazepine by oxcarbazepine. Epilepsia 36:810–816CrossRefPubMedGoogle Scholar
  85. 85.
    Man B, Brodie MJ, Kälviäinen R, Beran R; Berkovic S, Kruse T, Lyby K (1998) Laboratory variables in a comparative monotherapy drug trial with tiagabine (gabitril). Epilepsia 39:65Google Scholar
  86. 86.
    Doose DR, Gisclon LG, Liao S (1995) Pharmacokinetics of topiramate. Adv Antiepilep Drug Ther 1:7–16Google Scholar
  87. 87.
    Johannessen SI (1995) Pharmacokinetics and drug interactions: a non-issue for some new antiepileptic drugs? In: Topiramate in perspective, International Epileptology Symposium, London, pp 11–12Google Scholar
  88. 88.
    Ben-Menachem E, Axelsen M, Jonanson EH, Stagge A, Smith U (2003) Predictors of weight loss in adults with topiramate-treated epilepsy. Obesity Res 11:556–562Google Scholar
  89. 89.
    Mazzalovo E, Basso P, Vanzulli F, Mainini D, Morandi G, Mazzi C, Montanini R (1993) Hormonal modification in subjects with epilepsy treated with γ-vinyl GABA (vigabatrin). Epilepsia 34:121Google Scholar
  90. 90.
    Bianco E, Rodriguez-Mendizabal M, González-Correa JA, Mérida F, Lucena MI, Pavia J, Sánchez de la Cuesta F (1997) Effects of vigabatrine on the thyroid. Eur J Clin Pharmacol 52:PA 129, abstract 385Google Scholar
  91. 91.
    Krämer G, Kahaly G, Russ W, Beyer J (1997) Vigabatrin: endocrinal effects in healthy volunteers. Epilepsia 38:269–270CrossRefGoogle Scholar
  92. 92.
    Van Parys JAP, Meijer JWA, Edelbroek PM (1995) Comparison of enzyme induction by various antiepileptic drugs including oxcarbazepine and vigabatrin. Epilepsia 36:S161Google Scholar
  93. 93.
    Aanderud S, Standjord RE (1980) Hypothyroidisminduced by antiepiletpic therapy. Acta Neurol Scand 61:330–332PubMedCrossRefGoogle Scholar
  94. 94.
    Hegedus L, Hansen JM, Luhdorf K, Perrild J, Feldt-Rasmussen U, Kampmann JP (1985) Increased frequency of goitre in epileptic patients on long-term phenytoin or carbamazepine treatment. Clin Endocrinol (Oxf) 23:423Google Scholar
  95. 95.
    Bough EW, Crowley WF, Ridway EC, Walker H, Maloof F, Myers GS, Daniels GH (1978) Myocardial function in hypothyroidism. Relation to disease severity and response to treatment. Arch Intern Med 138:1476–1480CrossRefPubMedGoogle Scholar
  96. 96.
    Bockbrader HN, Posvar EL, Hunt T, Randinitis EJ (2004) Pregabalin does not alter the effectiveness of an oral contraceptive. Neurology, 62(7), suppl. 5 (abstract P04.097, 56th Annual Meeting of the American Academy of Neurology, San Francisco)Google Scholar
  97. 97.
    Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T (2004) Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). Epilepsy Res 61:1–48CrossRefPubMedGoogle Scholar
  98. 98.
    French JA, Kanner AM, Bautista J, Abou-Kahlil B, Browne T, Harden CL, Theodore WH, Bazil C, Stern J, Schachter SC, Bergen D, Hirtz D, Montouris GD, Nespeca M, Gidal B, Marks WJ, Turk WR, Fischer JH, Bourgeois B, Wilner A, Faught RE, Sachdeo RC, Beydoun A, Glauser TA (2004) Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 62:1252–1260PubMedGoogle Scholar
  99. 99.
    Capen CC (1994) Mechanisms of chemical injury of thyroid gland. Progr Clin Biol Res 387:173–191Google Scholar
  100. 100.
    Capen CC (1997) Mechanistic data and risk assessment of selected toxic end points of the thyroid gland. Toxicol Pathol 25:39–48PubMedCrossRefGoogle Scholar
  101. 101.
    Kato Y, Suzuki H, Ikushiro S, Yamada S, Degawa M (2005) Decrease in serum thyroxine levels by phenobarbital in rats is not necessarily dependent on increase in hepatic UDP–glucuronosyltransferase. Drug Metab Dispos 33:1608–1612CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • M. Strolin Benedetti
    • 1
  • R. Whomsley
    • 2
  • E. Baltes
    • 2
  • F. Tonner
    • 3
  1. 1.Drug Metabolism and PharmacokineticsUCB S.A.Nanterre CedexFrance
  2. 2.Drug Metabolism and PharmacokineticsUCB S.A.Braine l’AlleudBelgium
  3. 3.TA Neuro Psy DepartmentUCB Pharma S.A.Braine l’AlleudBelgium

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