Two cases of pregabalin neurotoxicity in chronic kidney disease patients.
Two cases of pregabalin neurotoxicity in chronic kidney disease patients.
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DOI：
10.1093/ndtplus/sfq219
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发表时间：
2011-04
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影响因子：
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通讯作者：
Park DJ
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作者：
Lee DW;Lee HJ;Kim HJ;Chang SH;Park DJ
先生，我们报告了两例新出现的慢性肾病（CKD）患者普瑞巴林神经毒性的病例。一名67岁男性被转诊至我院肾内科会诊。他因椎管狭窄住进骨科，并于5周前接受了手术。他三个月前开始进行血液透析。就诊时，他处于深度昏昏欲睡的精神状态。他还患有持续数天的全身性肌阵挛、失语症和构音障碍。我们没有通过磁共振成像或计算机断层扫描检测到脑部病变。没有给予任何可能引起他的神经症状和体征的药物。没有发现任何实验室异常可以解释他的神经功能缺陷。然而，就诊前2周开始普瑞巴林的剂量为300毫克/天，7天前剂量已增加至450毫克/天。我们得出的结论是，他的神经功能缺陷是普瑞巴林毒性的结果。立即停用普瑞巴林，并进行3次血液透析，患者神志清醒，全身肌阵挛、失语、构音障碍完全消失。第二个病例是一名 43 岁男性，因恶心、呕吐和全身无力而入院。他被诊断患有糖尿病和 CKD 4 期。入院三天后，他主诉颈后区域和双肩疼痛。他被诊断患有纤维肌痛并开始接受普瑞巴林治疗。接受75毫克/天剂量的普瑞巴林2天后，出现昏昏欲睡的精神状态，并检测到双上肢肌阵挛。根据 Cockcroft-Gault 公式计算出的肌酐清除率 (CCr) 为 25.7 mL/min。我们怀疑普瑞巴林有毒性，并立即撤回。此后，他从困倦、迷失方向和肌阵挛中完全康复。普瑞巴林口服吸收良好，生物利用度> 90%。不经过肝脏代谢，完全排泄至尿液中。通常建议 CCr 每下降 50%，普瑞巴林剂量就减少约 50%，以在肾功能受损患者中达到相似的血浆药物浓度 [1]。普瑞巴林对 CKD 患者的毒性的报道非常少[2-4]。 2 例发生在血液透析患者中，1 例发生在接受腹膜透析的患者中。我们的第一位患者也正在接受血液透析，而第二位患者是 CKD 4 期患者。据我们所知，尚无 4 期 CKD 患者出现普瑞巴林毒性的报道。在我们的第一个患者中，尽管普瑞巴林的初始剂量较高，但在剂量增加之前没有出现严重的症状和体征。这可能是通过定期血液透析去除药物的结果。尽管我们根据另一名患者的肾功能情况减少了普瑞巴林的剂量，但普瑞巴林的神经毒性确实发生了。我们认为，75 毫克/天的剂量可能不会使普瑞巴林的血清水平增加到足以引起神经功能损伤的程度，尽管我们没有测量血清中的药物水平。
Sir We report two cases of newly presenting pregabalin neurotoxicity in chronic kidney disease (CKD) patients. A 67-year-old man was referred to our nephrology department for consultation. He had been admitted to the department of orthopedics because of spinal stenosis and had undergone surgery 5 weeks earlier. He had started hemodialysis 3 months previously. Upon presentation, he was in a deep drowsy mental state. He was also suffering from generalized myoclonic jerk, aphasia and dysarthria of several days duration. We did not detect a brain lesion on magnetic resonance imaging or computed tomography. No medications were being given that could have induced his neurologic symptoms and signs. No laboratory abnormalities were detected that would explain his neurologic deficits. However, pregabalin had been started at a dosage of 300 mg/day 2 weeks before presentation, and the dosage had been increased to 450 mg/day 7 days previously. We concluded that his neurologic deficits were the result of pregabalin toxicity. Pregabalin was immediately withdrawn and an additional three hemodialysis sessions were performed, after which the patient became mentally alert and the generalized myoclonus, aphasia and dysarthria completely disappeared. The second case is that of a 43-year-old man who was admitted for evaluation of nausea, vomiting and general weakness. He was diagnosed with diabetes mellitus and CKD Stage 4. Three days after admission, he complained of pain around the posterior neck region and in both shoulders. He was diagnosed with fibromyalgia and commenced therapy with pregabalin. After receiving a 75 mg/day dose of pregabalin for 2 days, he developed a drowsy mental state and myoclonus of both upper extremities was detected. His calculated creatinine clearance (CCr) by Cockcroft–Gault formula was 25.7 mL/min. We suspected pregabalin toxicity and immediately withdrew it. Thereafter, he fully recovered from the drowsiness, disorientation and myoclonus. Pregabalin is well absorbed orally and has a bioavailability of> 90%. It is completely excreted into the urine without hepatic metabolism. It is usually suggested that pregabalin doses be decreased by∼ 50% for each 50% decline in CCr to achieve similar plasma drug concentrations in patients with impaired renal function [1]. Pregabalin toxicity in CKD patients has very rarely been reported [2–4]. Two cases have occurred in hemodialysis patients, whereas one case occurred in a patient undergoing peritoneal dialysis. Our first patient was also undergoing hemodialysis, whereas the second one was a CKD Stage 4 patient. To the best of our knowledge, there have been no reports of pregabalin toxicity in a Stage 4 CKD patient. In our first patient, although the initial dosage of pregabalin was high, there were no severe symptoms and signs before the increase in dosage. This might have been the result of drug removal by regular hemodialysis. Although we reduced the dosage of pregabalin in accordance with his renal function in the other patient, pregabalin neurotoxicity did occur. We think that a 75 mg/day dosage might not increase the serum level of pregabalin enough to induce neurologic impairment, although we did not measure the drug level in the serum.