Clinical pharmacokinetics of oxcarbazepine

Clinical Pharmacokinetics

Volumn 42, Issue 12, 2003, Pages 1023-1042

  May, Theodor W ^a,c   Korn Merker, Elisabeth ^b   Rambeck, Bernhard ^a  

^a Epilepsy Research Foundation   (Germany)

^b EPILEPSY CENTER BETHEL   (Germany)

^c Biochemisches Labor   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANALGESIC AGENT; ANTIDEPRESSANT AGENT; CALCIUM CHANNEL BLOCKING AGENT; CARBAMAZEPINE; CIMETIDINE; CITALOPRAM; CLOBAZAM; CLONAZEPAM; DEXTROPROPOXYPHENE; ERYTHROMYCIN; ETIRACETAM; FELBAMATE; FELODIPINE; GABAPENTIN; HALOPERIDOL; HISTAMINE H2 RECEPTOR ANTAGONIST; LAMOTRIGINE; LICARBAZEPINE; MACROLIDE; ORAL CONTRACEPTIVE AGENT; OXCARBAZEPINE; PHENAZONE; PHENOBARBITAL; PHENYTOIN; TOPIRAMATE; UNINDEXED DRUG; VALPROIC ACID; VERAPAMIL; VILOXAZINE; WARFARIN;

AGE DISTRIBUTION; ANALYTIC METHOD; ATAXIA; BIOTRANSFORMATION; BLOOD DYSCRASIA; CIRCADIAN RHYTHM; DOSE RESPONSE; DRUG ABSORPTION; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFECT; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MONITORING; DRUG STRUCTURE; DRUG TOLERABILITY; ELDERLY CARE; EPILEPSY; FATIGUE; HEADACHE; HUMAN; HYPONATREMIA; KIDNEY CLEARANCE; KIDNEY FAILURE; LEUKOPENIA; LIVER FAILURE; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; RASH; REVIEW; SINGLE DRUG DOSE; SOMNOLENCE; THROMBOCYTOPENIA; VERTIGO; VOLUNTEER; VOMITING;

ANTICONVULSANTS; CARBAMAZEPINE; CLINICAL TRIALS; DRUG ADMINISTRATION SCHEDULE; DRUG INTERACTIONS; DRUG MONITORING; EPILEPSIES, PARTIAL; HUMANS;

EID: 0141650365     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-200342120-00002     Document Type: Review

References (105)

1. Schmutz M, Brugger F, Gentsch C, et al. Oxcarbazepine: preclinical anticonvulsant profile and putative mechanisms of action. Epilepsia 1994; 35 Suppl. 5: S47-50
2. Volosov A, Xiaodong S, Perucca E, et al. Enantioselective pharmacokinetics of 10-hydroxycarbazepine after oral administration of oxcarbazepine to healthy Chinese subjects. Clin Pharmacol Ther 1999; 66 (6): 547-53
3. Schmidt D, Arroyo S, Baulac M, et al. Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view. Acta Neurol Scand 2001; 104 (3): 167-70
4. Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy 2001; 21 (8): 904-19
5. Castillo S, Schmidt DB, White S. Oxcarbazepine add-on for drug-resistant partial epilepsy (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2001
6. Shorvon S. Oxcarbazepine: a review. Seizure 2000; 9: 75-9
7. Smith PE. Clinical recommendations for oxcarbazepine (for the UK Oxcarbazepine Advisory Board). Seizure 2001; 10 (2): 87-91
8. Faigle JW, Menge GP. Pharmacokinetic and metabolic features of oxcarbazepine and their clinical significance: comparison with carbamazepine. Int Clin Psychopharmacol 1990; 5: 73-82
9. Bialer M. Oscarbazepine - chemistry, biotransformation and pharmacokinetics. Chapter 45. In: Levy EH, Mattson R, Meldrum BS, et al., editors. Antiepileptic Drugs. Philadelphia: Lippincott-Williams adn Wilkins, 2002: 459-65
10. von Unruh GE, Paar WD. Gas chromatographic assay for oxcarbazepine and its main metabolites in plasma. J Chromatogr 1985; 345 (1): 67-76
11. Menge G, Dubois JP. Determination of oxcarbazepine in human plasma by high-performance liquid chromatography. J Chromatogr 1983; 275 (1): 189-94
12. Juergens U. HPLC analysis of antiepileptic drugs in blood samples: microbore separation of fourteen compounds. J Liquid Chromatogr 1987; 10 (2 & 3): 507-32
13. Elyas AA, Goldberg VD, Patsalos PN. Simple and rapid microanalytical high-performance liquid chromatographic technique for the assay of oxcarbazepine and its primary active metabolite 10-hydroxycarbazepine. J Chromatogr 1990; 528 (2): 473 -9
14. Rouan MC, Decherf M, Le Clanche V, et al. Automated microanalysis of oxcarbazepine and its monohydroxy and transdiol metabolites in plasma by liquid chromatography. J Chromatogr B Biomed Appl 1994; 658 (1): 167-72
15. Matar KM, Nicholls PJ, al-Hassan MI, et al. A rapid micromethod for simultaneous measurement of oxcarbazepine and its active metabolite in plasma by high-performance liquid chromatography. J Clin Pharm Ther 1995; 20 (4): 229-34
16. Levert H, Odou P, Robert H. LC determination of excarbazepine and its active metabolite in human serum. J Pharm Biomed Anal 2002; 28: 517-25
17. von Unruh GE, Paar WD. Gas chromatographic/mass spectrometric assays for oxcarbazepine and its main metabolites, 10-hydroxy-carbazepine and carbaze-pine-10,11-trans-diol. Biomed Environ Mass Spectrom 1986; 13 (12): 651-6
18. Flesch G, Francotte E, Hell F, et al. Determination of the R-(-) and S-(+) enantiomers of the monohydroxylated metabolite of oxcarbazepine in human plasma by enantioselective high-performance liquid chromatography. J Chromatogr 1992; 581 (1): 147-51
19. Feldmann KF, Dörhöfer G, Faigle JW, et al. Pharmacokinetics and metabolism of GP 47 779, the main human metabolite of oxcarbazepine (GP 47 680) in animals and healthy volunteers. In: Dam M, Gram L, Penry JK, editors. Advances in epileptology: XIIth Epilepsy International Symposium. New York: Raven Press, 1981: 89-96
20. 14C-oxcarbazepine in man. Xenobiotica 1986; 16 (8): 769-78
21. Baruzzi A, Albani F, Riva R. Oxcarbazepine: pharmacokinetic interactions and their clinical relevance. Epilepsia 1994; 35 Suppl. 3: S14-9
22. Rouan MC, Lecaillon JB, Godbillon J, et al. The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites. Eur J Clin Pharmacol 1994; 47 (2): 161-7
23. 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 (4): 366-8
24. Jung H, Noguez A, Mayer L, et al. The distribution of 10-hydroxy carbazepine in blood compartments. Biopharm Drug Dispos 1997; 18 (1): 17-23
25. Kristensen O, Klitgaard NA, Jonsson B, et al. Pharmacokinetics of 10-OH-carbazepine, the main metabolite of the antiepileptic oxcarbazepine, from serum and saliva concentrations. Acta Neurol Scand 1983; 68 (3): 145-50
26. van Heiningen PN, Eve MD, Oosterhuis B, et al. The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine. Clin Pharmacol Ther 1991; 50 (4): 410-9
27. Degen PH, Flesch G, Cardot JM, et al. The influence of food on the disposition of the antiepileptic oxcarbazepine and its major metabolites in healthy volunteers. Biopharm Drug Dispos 1994; 15 (6): 519-26
28. Flesch G, Tudor D, Souppart C, et al. Oxcarbazepine final market image tablet formulation bioequivalence study after single administration and at steady state in healthy subjects. Int J Clin Pharmacol Ther 2002; 40: 524-32
29. Hooper WD, Dickinson RG, Dunstan PR, et al. Oxcarbazepine: preliminary clinical and pharmacokinetic studies on a new anticonvulsant. Clin Exp Neurol 1987; 24: 105-12
30. Dickinson RG, Hooper WD, Dunstan PR, et al. First dose and steady-state pharmacokinetics of oxcarbazepine and its 10-hydroxy metabolite. Eur J Clin Pharmacol 1989; 37 (1): 69-74
31. Theisohn M, Heimann G. Disposition of the antiepileptic oxcarbazepine and its metabolites in healthy volunteers. Eur J Clin Pharmacol 1982; 22 (6): 545-51
32. Grant SM, Faulds D. Oxcarbazepine: a review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders. Drugs 1992; 43 (6): 873-88
33. Krämer G. Oxcarbazepin (Trileptal): ein neues antiepileptikum zur mono- und kombinationstherapie. Akt Neurologie 2000; 27: 59-71
34. Klitgaard NA, Kristensen O. Use of saliva for monitoring oxcarbazepine therapy in epileptic patients. Eur J Clin Pharmacol 1986; 31 (1): 91-4
35. Patsalos PN, Elyas AA, Zakrzewska JM. Protein binding of oxcarbazepine and its primary active metabolite, 10-hydroxy-carbazepine, in patients with trigeminal neuralgia. Eur J Clin Pharmacol 1990; 39 (4): 413-5
36. May TW, Rambeck B, Sälke-Kellermann A. Fluctuations of 10-hydroxy-carbazepine during the day in epileptic patients. Acta Neurol Scand 1996; 93 (6): 393-7
37. Christensen J, Hojskov CS, Dam M, et al. Plasma concentration of topiramate correlates with cerebrospinal fluid concentration. Ther Drug Monit 2001; 23 (5): 529-35
38. Kumps A, Wurth C. Oxcarbazepine disposition: preliminary observations in patients. Biopharm Drug Dispos 1990; 11: 365-70
39. Gonzalez-Esquivel DF, Ortega-Gavilan M, Alcantara-Lopez G, et al. Plasma level monitoring of oxcarbazepine in epileptic patients. Arch Med Res 2000; 31 (2): 202-5
40. Viola MS, Bercellini MA, Saidon P, et al. Pharmacokinetic variability of oxcarbazepine in epileptic patients. Medicina (B Aires) 2000; 60 (6): 914-8
41. Sachdeo R, Beydoun A, Schachter S, et al. Oxcarbazepine (Trileptal) as monotherapy in patients with partial seizures. Neurology 2001; 57 (5): 864-71
42. Larkin JG, McKee PJ, Forrest G, et al. Lack of enzyme induction with oxcarbazepine (600mg daily) in healthy subjects. Br J Clin Pharmacol 1991; 31 (I): 65-71
43. Krämer G, Theisohn M, Stoll KD, et al. Oxcarbazepin versus Carbamazepin bei gesunden Probanden. Studien zur Kinetik, zu Metabolismus und Verträglichkeit. In: Kruse R, editor. Epilepsie 84. Reinbek: Einhom, 1985: 379-87
44. Novartis Pharmaceuticals. Trileptal® (oxcarbazepine): prescribing information. East Hanover, NJ: Novartis Pharmaceuticals, Inc., 2001
45. McKee PJ, 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 (1): 27-32
46. Lloyd P, Flesch G, Dieterle W. Clinical pharmacology and pharmacokinetics of oxcarbazepine. Epilepsia 1994; 35 Suppl. 3: S10-3
47. Hulsman JARJ, Rentmeester TW, Banfield CR, et al. Effects of felbamate on the pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbaze, pine. Clin Pharmacol Ther 1995; 58 (4): 383-9
48. Arnoldussen W, Hulsman J, Rentmeester T. Interaction between oxcarbazepine and phenytoin [abstract]. Epilepsia 1993; 34 Suppl. 6: 37
49. Arnoldussen W, Hulsman J, Rentmeester T. Oxcarbazepine (OCBZ) twice daily is as effective as OCBZ three times daily: a clinical and pharmacokinetic study of 24 volunteers and 6 patients [abstract]. Epilepsia 1991; 32 Suppl. 1: 69
50. van Parys JA, Hop W, Vulto A, et al. Steady-state pharmacokinetics of oxcarbazepine in adults [abstract]. Epilepsia 1998; 39 Suppl. 6: 47
51. Pariente-Khayat A, Fran A, Vauzelle-Kervroedan F, et al. Pharmacokinetics of oxcarbazepine as add-on therapy in epileptic children [abstract]. Epilepsia 1994; 35 Suppl. 8: 119
52. Dulac O, D'Souza J, Motte J. Multicenter study of oxcarbazepine pharmacokinetics and tolerability in children with refractory epilepsy [abstract]. Ann Neurol 2001; 50: S104
53. Stroink H, Tang KT, van Parys JAP, et al. Steady-state pharmacokinetics of oxcarbazepine in children [abstract]. Epilepsia 1998; 39 Suppl. 6: 48
54. Bülau P, Paar WD, von Unruh GE. Pharmacokinetics of oxcarbazepine and 10-hydroxy-carbazepine in the newborn child of an oxcarbazepine-treated mother. Eur J Clin Pharmacol 1988; 34 (3): 311-3
55. Bar-Oz B, Nulman I, Koren G, et al. Anticonvulsants and breast feeding: a critical review. Paediatr Drugs 2000; 2 (2): 113-26
56. Myllynen P, Pienimaki P, Jouppila P, et al. Transplacental passage of oxcarbazepine and its metabolites in vivo. Epilepsia 2001; 42 (11): 1482-5
57. Pienimaki P, Lampela E, Hakkola J, et al. Pharmacokinetics of oxcarbazepine and carbamazeplne in human placenta. Epilepsia 1997; 38 (3): 309-16
58. Saano V, Schurr-Eisinger S, Möbius HJ, et al. Effect of oxcarbazepine on antipyrine metabolism in healthy volunteers [abstract]. Epilepsia 1995; 36 Suppl. 3: 161
59. Brookman LJ, Lloyd P, Lecaillon JB, et al. Single-center, open-label, placebo-controlled trial to determine the effects of 900mg oxcarbazepine twice daily on markers of enzyme induction in healthy male volunteers [abstract]. Epilepsia 1995; 36 Suppl. 3: 161
60. Keränen T, Möbius HJ, Schurr-Eisinger S, et al. Effect of oxcarbazepine on hepatic clearance of antipyrine in patients with previously untreated epilepsy [abstract]. Epilepsia 1995; 36 Suppl. 3: 161
61. Lakehal F, Wurden CJ, Kalhom TF, et al. Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. Epilepsy Res 2002; 52: 79-83
62. Tripp SL, Hundal J, Kapeghain JC, et al. Evaluation of oxcarbazepine and its mono-hydroxy metabolite (GP 47779), for potential drug interactions in vitro [abstract]. Epilepsia 1996; 37 Suppl. 5: 22
63. May TW, Rambeck B, Jürgens U. Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Ther Drug Monit 1999; 21 (2): 175-81
64. Barcs G, Walker EB, Elger CE, et al. Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy. Epilepsia 2000; 41 (12): 1597-607
65. Sallas W. Population pharmacokinetics analysis of oxcarbazepine (Trileptal) in children with epilepsy [abstract]. Epilepsia 1999; 40 Suppl. 7: 102
66. van Parys JAP, Meijer JWA, Segers JP. Dose-concentration proportionality in epileptic patients stabilized on oxcarbazepine: effects of co-medication [abstract]. Epilepsia 1991; 32 Suppl. 1: 70
67. Arnoldussen W, Hulsman J, Rentmeester T. The interaction of valproate and clobazam on the metabolism of oxcarbazepine [abstract]. Epilepsia 1993; 34 Suppl. 2: 160
68. Hossain M, Sallas W, Gasparini M, et al. Drug-drug interaction profile of oxcarbazepine in children and adults [abstract]. Neurology 1999; 52 Suppl. 2: A525
69. Rambeck B, Salke-Treumann A, May TW, et al. Valproic acid-induced carbamazepine-10,11-epoxide toxicity in children and adolescents. Eur Neurol 1990; 30 (2): 79-83
70. 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 (5): 376-9
71. Fröscher W, Blankenhorn V, May TW, et al. Pharmakotherapie der Epilepsien. 3rd ed. Stuttgart: Schattauer, 2000
72. Krämer G, Tettenborn B, Flesch G. Oxcarbazepine-verapamil drug interaction study in healthy volunteers [abstract]. Epilepsia 1991; 32 Suppl. 1: 70
73. 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 (1): 14-7
74. 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 (2): 130-3
75. Keränen T, Jolkkonen J, Klosterskov-Jensen P, et al. Oxcarbazepine does not interact with cimetidine in healthy volunteers. Acta Neurol Scand 1992; 85 (4): 239-42
76. Keränen T, Jolkkonen J, Jensen PK, et al. Absence of interaction between oxcarbazepine and erythromycin. Acta Neurol Scand 1992; 86 (2): 120-3
77. May TW, Rambeck B, Juurgens U. Serum concentrations of levetiracetam in epileptic patients: the influence of dose and comedication. Ther Drug Monit. In Press.
78. May TW, Rambeck B, Jürgens U. Serum concentrations of topiramate in epileptic patients: the influence of dose, age and comedication. Ther Drug Monit 2002; 24 (3): 366-74
79. Houtkooper MA, Lammertsma A, Meyer JW, et al. Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine? Epilepsia 1987; 28 (6): 693-8
80. Isojärvi JI, Pakarinen AJ, Rautio A, et al. Liver enzyme induction and serum lipid levels after replacement of carbamazepine with oxcarbazepine. Epilepsia 1994; 35 (6): 1217-20
81. Krämer G, Tettenborn B, Klosterskov-Jensen P, et al. Oxcarbazepine does not affect the anticoagulant activity of warfarin. Epilepsia 1992; 33 (6): 1145-8
82. 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 (1): 39-42
83. Sonnen AEH. Oxcarbazepine and oral contraceptives [abstract]. Acta Neurol Scand 1990; 82 Suppl. 133: 37
84. Klosterskov JP, Saano V, Haring P, et al. Possible interaction between oxcarbazepine and an oral contraceptive. Epilepsia 1992; 33 (6): 1149-52
85. Fattore C, Cipolla G, Gatti G, et al. Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia 1999; 40 (6): 783-7
86. Leinonen E, Lepola U, Koponen H. Substituting carbamazepine with oxcarbazepine increases citalopram levels: a report on two cases. Pharmacopsychiatry 1996; 29 (4): 156-8
87. Raitasuo V, Lehtovaara R, Huttunen MO. Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics: a case report. Psychopharmacology 1994; 116 (1): 115-6
88. Roesche J, Fröscher W, Abendroth D, et al. Possible oxcarbazepine interaction with cyclosporine serum levels: a single case study. Clin Neuropharmacol 2001; 24 (2): 113-6
89. Sabers A, Gram L. Newer anticonvulsants: comparative review of drug interactions and adverse effects. Drugs 2000; 60 (1): 23-33
90. Korn-Merker E. Indikationen, Wirksamkeit und Verträglichkeit von Oxcarbazepin in der Mono- und Kombinationstherapie bei Kindern mit Epilepsie. In: Aksu F, editor. Aktuelle Neuropädiatrie 2001. Nürnberg: Novartis Pharma Verlag, 2002: 526-36
91. Gates JR, Sachdeo RC, Graham SM, et al. Enzymatic induction and tolerability in transition to oxcarbazepine in the STOPS trials [abstract]. Epilepsia 2001; 42 Suppl. 7: 254
92. Edelbroek PM, Augustijn PB, DeHaan GJ, et al. Change in oxcarbazepine (Trileptal®) formulation is associated with more side effects and higher blood concentrations. J Neurol Neurosurg Psychiatry 2001; 71 (5): 708-9
93. Flesch G, Tudor D, Denouel J, et al. Assessment of the bioequivalence of two oxcarbazepine oral suspensions versus a film-coated tablet in healthy subjects. Int J Clin Pharmacol Ther 2003; 41: 299-308
94. van der Kuy PH, Koppejan EH, Wirtz JJ. Rectal absorption of oxcarbazepine. Pharm World Sci 2000; 22 (4): 165-6
95. Augusteijn R, van Parys JAP. Oxcarbazepine (Trileptal, OXC): dose-concentration relationship in patients with epilepsy [abstract]. Acta Neurol Scand 1990; 82 Suppl. 133: 37
96. Dam M, Ekberg R, Loyning Y, et al. A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Epilepsy Res 1989; 3: 70-6
97. Nedelman JR, Hossain M, Chang SW, et al. Oxcarbazepine: analysis of concentration-efficacy/safety relationships [abstract]. Neurology 1999; 52 Suppl. 2: A524
98. Fröscher W, Krämer G, Schmidt D, et al. Serumkonzentrationen von Antiepileptika [Serum concentration of anticonvulsants: practical guidelines for measuring and useful interpretation: therapy Committee of the German Section of the International Epilepsy League]. Nervenarzt 1999; 70 (2): 172-7
99. Bourgeois BFD. Pharmacokinetic properties of current antiepileptic drugs: what improvements are needed? Neurology 2000; 55 (11): S11-6
100. Tomson T, Johannessen SI. Therapeutic monitoring of the new antiepileptic drugs. Eur J Clin Pharmacol 2000; 55 (10): 697-705
101. Borusiak P, Korn-Merker E, Holert N, et al. Oxcarbazepine in treatment of childhood epilepsy: a survey of 46 children and adolescents. J Epilepsy 1998; 11: 355-60
102. Johannessen SI, Battino D, Berry DJ, et al. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther Drug Monit 2003; 25 (3): 347-63
103. Tecoma ES. Oxcarbazepine. Epilepsia 1999; 40:S37-46
104. Cardot JM, Degen P, Flesch G, et al. Comparison of plasma and saliva concentrations of the active monohydroxy metabolite of oxcarbazepine in patients at steady state. Biopharm Drug Dis 1995; 16 (7): 603-14
105. Palm R, Nilsson HL, Klosterskov-Jensen P, et al. Diurnal plasma concentrations profiles of oxcarbazepine: comparison between administration twice and three times daily [abstract]. Epilepsia 1991; 32 Suppl. 1: 69