ACYCLOVIR-INDUCED NEUROTOXICITY - CONCENTRATION-SIDE-EFFECT RELATIONSHIP IN ACYCLOVIR OVERDOSE
ACYCLOVIR-INDUCED NEUROTOXICITY - CONCENTRATION-SIDE-EFFECT RELATIONSHIP IN ACYCLOVIR OVERDOSE
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DOI：
10.1016/0002-9343(93)90186-s
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发表时间：
1993-02-01
影响因子：
5.9
通讯作者：
RITZ, RF
中科院分区：
文献类型：
--
作者：
HAEFELI, WE;SCHOENENBERGER, RAZ;RITZ, RF
目的：探讨阿昔洛韦严重神经毒性患者的剂量-副作用关系，总结文献中有关阿昔洛韦引起中枢神经系统副作用的文献资料。方法：对一例严重阿昔洛韦过量并出现昏迷和非少尿性肾功能衰竭的患者进行重复采血。放射免疫法测定的阿昔洛韦浓度与意识水平有关。结果：我们测得的阿昔洛韦血药浓度为迄今报道的最高水平(229.9摩尔/L=51.8 mg/L)。意识障碍在血药浓度峰值出现后有24至48小时的显著时间延迟，在达到治疗范围后相应延迟消失(逆时针方向滞后)。停药6天后，中枢神经系统症状缓解，4天后，肾功能恢复到治疗前水平。结论：阿昔洛韦血药浓度高峰后24~48小时出现神经毒性，可以解释类似病例中报道的阿昔洛韦浓度范围较大的原因。因此，单一药物水平的测量可能没有什么诊断价值。由于毒性的发展有明显的延迟，及早去除药物(通过血液透析)可能会预防中枢神经毒性。
PURPOSE: To investigate the concentration-side effect relationship in a patient with severe acyclovir-induced neurotoxicity and to summarize the information available in the literature about central nervous system side effects due to acyclovir.METHODS: Repeated blood samples were drawn in a patient with severe acyclovir overdose who developed coma and nonoliguric renal failure. The acyclovir levels measured by radioimmunoassay were related to the level of consciousness. RESULTS: We measured the highest acyclovir serum levels reported so far (229.9 mumol/L = 51.8 mg/L). Impairment of consciousness developed with a remarkable temporal delay of 24 to 48 hours after occurrence of peak serum concentrations and resolved with a comparable delay after reaching the therapeutic range (anticlockwise hysteresis). Six days after discontinuation of the drug, central nervous system symptoms had resolved, and, 4 days later, renal function returned to pretreatment values. CONCLUSIONS: The observation that neurotoxicity developed with a delay of 24 to 48 hours after acyclovir peak serum concentrations could explain the wide range of acyclovir levels reported in similar cases. Single drug level measurements may therefore be of little diagnostic value. Since toxicity develops with a remarkable delay, early removal of the drug (by hemodialysis) could possibly prevent central nervous toxicity.