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卡马西平和奥卡西平治疗期间血小板计数与日剂量以及卡马西平、卡马西平-10,11-环氧化物和10-羟基卡马西平血清浓度的关系。

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.

作者信息

Tutor-Crespo Maria J, Hermida Jesus, Tutor Jose C

机构信息

Unidad Monitorización Fármacos, Laboratorio Central, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain.

出版信息

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007 Jun;151(1):91-4. doi: 10.5507/bp.2007.016.

Abstract

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 10(9)/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.

摘要

背景

卡马西平(CBZ)偶尔会引起血液系统疾病,如血小板减少症,最近有一例奥卡西平(OXCBZ)诱发血小板减少症的病例报道。我们研究的目的是测定接受CBZ和OXCBZ治疗的癫痫患者的血小板计数,以及其与这些药物及其代谢产物的剂量和血清水平的关系。

方法

测定了137例接受CBZ治疗的患者以及60例接受OXCBZ治疗的患者的CBZ及其环氧化物的血清水平,以及OXCBZ的药理活性单羟基衍生物的血清水平。还测定了血小板计数、平均血小板体积和血小板体积分布宽度。

结果

接受CBZ和OXCBZ治疗的患者组之间的血小板计数差异不显著。未发现血小板计数与所给予的抗癫痫药物及其代谢产物的血清水平之间存在显著相关性。然而,血小板计数与CBZ和OXCBZ的每日剂量之间存在显著的负相关性(p<0.01)。有5例患者(4例接受CBZ治疗,1例接受OXCBZ治疗)的血小板计数<150×10⁹/L。

结论

根据平均血小板体积和血小板分布宽度,在部分研究患者中观察到的血小板减少症是由于外周血血小板过度破坏所致。然而,所得结果表明,CBZ或OXCBZ诱发血小板减少症的机制并非由于这些药物或其主要代谢产物对循环血小板的直接毒性。虽然接受OXCBZ治疗的患者血小板减少症的患病率(1.7%)低于接受CBZ治疗的患者(2.9%),但仍建议对接受这两种药物治疗的患者进行常规血小板计数监测。

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