Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007, 151(1):91-94 | DOI: 10.5507/bp.2007.016
Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10, 11-epoxide, and 10-hydroxycarbazepine
- Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain
Background: Carbamazepine (CBZ) occasionally causes haematological disorders such as thrombocytopenia, and recently a case of oxcarbazepine (OXCBZ)-induced thrombocytopenia has been described. The aim of our study was blood platelet count determination in epileptic patients treated with CBZ and OXCBZ, and its relationship with the dose and serum levels of these drugs and its metabolites.
Methods: The serum levels of CBZ and its epoxide, and the pharmacologically active monohydroxy derivative of OXCBZ were determined in 137 patients treated with CBZ, and 60 patients treated with OXCBZ. The platelet count, mean platelet volume, and platelet size distribution width were also determined.
Results: The difference between the platelet counts of the patient groups treated with CBZ and OXCBZ was not significant. No significant correlations between the platelet count and serum levels of the administered antiepileptic drugs and their metabolites were found. However, significant negative correlations between the platelet count and the daily doses of CBZ and OXCBZ were obtained (p < 0.01). In 5 cases (4 treated with CBZ and 1 with OXCBZ) the platelet count was < 150 x 109/l.
Conclusions: In accordance with the mean platelet volume and platelet distribution width, the thrombocytopenia observed in some of the patients studied was due to a hyper-destruction of peripheral blood platelets. However, the results obtained suggest that the mechanism of CBZ or OXCBZ-induced thrombocytopenia is not due to a direct toxicity of these drugs or their major metabolites on the circulating platelets. Although, the patients treated with OXCBZ shown a lower prevalence for thrombocytopenia (1.7 %) than those treated with CBZ (2.9 %), the routine platelet count monitoring in patients treated with both drugs may be recommended.
Keywords: Carbamazepine, Oxcarbazepine, Platelet count, Mean platelet volume, Platelet distribution width
Received: April 30, 2007; Accepted: May 20, 2007; Published: June 1, 2007 Show citation
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References
- Schmidt D, Elger CE. What is the evidence that oxcarbazepine and carbamazepine are distinctly antiepileptic drugs. Epilepsy Behav 2004; 5:32735. Go to original source... Go to PubMed...
- Andreasen AH, Brosen K, Damkier P. A comparative pharmacokinetic study in healthy volunte4rs of the eff ect of carbamazepine and oxcarbazepine on cyp3a4. Epilepsia 2007; 48:49096. Go to original source... Go to PubMed...
- Ishikita T, Ishiguro A, Fujisawa K, Tsukimoto I, Shimbo T. Carbamazepine-induced thrombocytopenia defi ned by a challenge test. Am J Hematol 1999; 62:5255. Go to original source... Go to PubMed...
- Kimura M, Yoshino K, Maeoka Y, Suzuki N. Carbamazepine-induced thrombocytopenia and carbamazepine-10,11-epoxide: a case report. Psychiatry Clin Neurosci 1995; 49:6970. Go to original source... Go to PubMed...
- Goraya JS, Virdi VS. Carbamazepine-induced immune thrombocytopenia. Neurol India 2003; 51:132133.
- Drury I, Vanderzant CW. Carbamazepine-induced isolated thrombocytopenia. Am J Psychiatry 1988; 145:1034. Go to original source... Go to PubMed...
- Terao T. Trasient thrombocytopenia while continuing carbamazepine. Am J Psychiatry 1993; 150:1750. Go to original source... Go to PubMed...
- Novartis Pharmaceuticals Corporation. Trileptal (oxcarbazepine). Rev: January 2006. [www.pharma.us.novartis.com/product/pi/pdf/ trileptal.pdf].
- Mahmud J, Mathews M, Verma S, Basil B. Oxcarbazepine-induced thrombocytopenia. Psychosomatics 2006; 47:7374. Go to original source... Go to PubMed...
- Mendez-Alvarez E, Soto-Otero R, Sierra-Marcuño G. The effect of storage conditions on the stability of carbamazepine and carbamazepine-10,11-epoxide in plasma. Clin Chim Acta 1986; 154:24346. Go to original source... Go to PubMed...
- Nirogi RV, Randikere VN, Shukla M, Mudigonda J, Ajjala DR. Quantifi cation of oxcarbazepine and its active metabolite 10-hydroxycarbazepine in human plasma by high-performance liquid chromatography. Arzneimittelforschung 2006; 56:51723. Go to original source...
- Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E et al. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have suffi cient sensitivity and specifi city in the diagnosis on immune thrombocytopenia. Br J Haematol 2005; 128:698702. Go to original source... Go to PubMed...
- Bowles KM, Cooke LJ, Richards EM, Baglin TP. Platelet size has diagnostic predictive value in patients with thrombocytopenia. Clin Lab Haematol 2005; 27:37073. Go to original source... Go to PubMed...
- Osselaer JC, Lamart J, Scheiff JM. Platelet distribution width for diff erential diagnosis of thrombocytosis. Clin Chem 1997; 43:1072 76. Go to original source...
- Kumar S. Anticonvulsivant-hypersensitivity syndrome in a child. Neurol India 2003; 51:427.
- Shechter Y, Brenner B, Klein E, Tatarsky I. Carbamazepine (Tegretol)-induced thrombocytopenia. Vox Sang 1993; 65:328 30. Go to original source... Go to PubMed...
- Kornberg A, Kobrin I. IgG antiplatelet antibodies due to carbamazepine. Acta Haematol 1982; 68:6870. Go to original source... Go to PubMed...
- Pellock JM, Willmore LJ. A rational guide to routine blood monitoring in patients receiving antiepileptic drugs. Neurology 1991; 41:96164. Go to original source... Go to PubMed...
- Oyewumi LK, Cernovsky ZZ, Freeman DJ, Streiner DL. Relation of blood counts during clozapine treatment to serum concentrations of clozapine and nor-clozapine. Can J Psychiatry 2002; 47:25761. Go to original source... Go to PubMed...
- Brummitt DR, Barker HF. The determination of a reference range for new platelet parameters produced by the Bayer AdviaTM 120 full blood analyser. Clin Lab Haematol 2000; 22:1037. Go to original source... Go to PubMed...
- Raebel M, Lyons EE, Andrade SE, Chan KA, Chester EA et al. Laboratory monitoring of drugs at initiation of therapy in ambulatory care. J Gen Intern Med 2005; 20:112026. Go to original source... Go to PubMed...
- Hurley JS, Roberts M, Solberg LI, Gunter MJ, Nelson WW, Young L et al. Laboratory safety monitoring of chronic medications in ambulatory care settings. J Gen Intern Med 2005; 20:33133. Go to original source... Go to PubMed...