Pharmacokinetics and effects of ribavirin following intraventricular administration for treatment of subacute sclerosing panencephalitis
Pharmacokinetics and effects of ribavirin following intraventricular administration for treatment of subacute sclerosing panencephalitis
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DOI：
10.1128/aac.48.12.4631-4635.2004
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发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Suzuki, H
中科院分区：
文献类型：
--
作者：
Hosoya, M;Mori, S;Suzuki, H
利巴韦林是一种广谱抗病毒药物，对包括麻疹病毒在内的许多RNA病毒具有抑制活性。本文报告5例亚急性硬化性全脑炎（SSPE）患者，经脑室内注射利巴韦林治疗。虽然利巴韦林有短暂的副作用，如嗜睡，头痛，嘴唇和牙龈肿胀，结膜充血，脑室内利巴韦林治疗通常是安全的，耐受性良好。单次脑室内给药后，脑脊液（CSF）利巴韦林浓度下降，如单指数函数所述。然而，在峰值水平和半衰期方面存在相当大的个体间变异性。我们的目的是根据CSF中利巴韦林的峰值水平和半衰期调整脑室内给药的个体剂量和频率，以将CSF利巴韦林浓度维持在目标水平。在5例患者中的4例中观察到临床有效性（神经功能显著改善和/或CSF中麻疹病毒血凝抑制抗体滴度显著降低）。对于这4例患者，CSF利巴韦林浓度维持在体外和体内几乎完全抑制SSPE病毒复制的水平，而无临床改善的患者的浓度较低。这些结果表明，如果CSF利巴韦林浓度维持在高水平，则脑室内给予利巴韦林对SSPE有效。脑室内利巴韦林治疗SSPE患者的潜在用途应进一步追求，并可能应用于其他RNA病毒引起的脑炎患者的治疗。
Ribavirin is a broad-spectrum antiviral drug with inhibitory activity against many RNA viruses, including measles virus. Five patients with subacute sclerosing panencephalitis (SSPE) were treated with ribavirin by intraventricular administration. Although there were transient side effects attributed to ribavirin, such as drowsiness, headache, lip and gingival swelling, and conjunctival hyperemia, intraventricular ribavirin therapy was generally safe and well tolerated. The cerebrospinal fluid (CSF) ribavirin concentration decreased, as described by a monoexponential function, after a single intraventricular dose. There was considerable inter-individual variability, however, in the peak level and half-life. We aimed to adjust the individual dose and frequency of intraventricular administration based on the peak level and half-life of ribavirin in the CSF in order to maintain the CSF ribavirin concentration at the target level. Clinical effectiveness (significant neurologic improvement and/or a significant decrease in titers of hemagglutination inhibition antibodies against measles virus in CSF) was observed for four of five patients. For these four patients, CSF ribavirin concentrations were maintained at a level at which SSPE virus replication was almost completely inhibited in vitro and in vivo, whereas the concentration was lower in the patient without clinical improvement. These results suggest that intraventricular administration of ribavirin is effective against SSPE if the CSF ribavirin concentration is maintained at a high level. Intraventricular ribavirin therapy should be pursued further for its potential use for patients with SSPE and might be applied in the treatment of patients with encephalitis caused by other RNA viruses.