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戊巴比妥的治疗药物监测:一所学术医疗中心的经验

Therapeutic Drug Monitoring of Pentobarbital: Experience at an Academic Medical Center.

作者信息

Humble Robert M, Ehlers Alexandra, Pakalniskis Brittany L, Morris Cory, Drees Denny, Kulhavy Jeff, Krasowski Matthew D

机构信息

Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

出版信息

Ther Drug Monit. 2015 Dec;37(6):783-91. doi: 10.1097/FTD.0000000000000217.

Abstract

BACKGROUND

Pentobarbital is used for management of intractable seizures and for reducing elevated intracranial pressure. Dosing of pentobarbital can be aided by therapeutic drug monitoring (TDM). There is no commercially available automated assay for measurement of pentobarbital serum/plasma concentrations; consequently, chromatography-based assays are often used.

METHODS

Pentobarbital TDM was studied over a 14-year period at an academic medical center. 154 patients (94 adult, 60 pediatric) were identified who had pentobarbital levels ordered at least once during a hospital encounter. Chart review included patient diagnosis, indication for pentobarbital therapy, recent or concomitant medication with other barbiturates, patient disposition, organ donation, pentobarbital dosing changes, and neurosurgical procedures. Pentobarbital serum/plasma concentrations were determined on an automated clinical chemistry platform with a laboratory-developed test adapted from a urine barbiturates immunoassay.

RESULTS

Chart review showed therapeutic use of pentobarbital generally consistent with previously published literature. The most common errors observed involved confusion in barbiturate names (eg, mix-up of pentobarbital and phenobarbital in test ordering or in provider notes) that seemed to have minimal impact on TDM effectiveness, with pentobarbital serum/plasma concentrations generally within target ranges. The laboratory-developed pentobarbital immunoassay showed cross-reactivity with phenobarbital and butalbital that was eliminated by alkaline and heat pretreatment. The immunoassay was linear to 20 mcg/mL and correlated closely with gas chromatography-mass spectrometry measurements at a reference laboratory.

CONCLUSIONS

Pentobarbital TDM can be performed by immunoassay on an automated clinical chemistry platform, providing an alternative to chromatography-based methods. Confusion in barbiturate names is common, especially pentobarbital and phenobarbital.

摘要

背景

戊巴比妥用于治疗难治性癫痫和降低颅内压升高。戊巴比妥的给药可通过治疗药物监测(TDM)辅助。目前尚无用于测量戊巴比妥血清/血浆浓度的商业自动化检测方法;因此,常使用基于色谱的检测方法。

方法

在一家学术医疗中心对戊巴比妥TDM进行了为期14年的研究。确定了154例患者(94例成人,60例儿童),他们在住院期间至少有一次进行了戊巴比妥水平检测。病历审查包括患者诊断、戊巴比妥治疗的指征、近期或同时使用的其他巴比妥类药物、患者处置、器官捐赠、戊巴比妥给药变化以及神经外科手术。戊巴比妥血清/血浆浓度在自动化临床化学平台上通过一种基于尿液巴比妥类免疫测定法改编的实验室自行开发的检测方法进行测定。

结果

病历审查显示戊巴比妥的治疗用途总体上与先前发表的文献一致。观察到的最常见错误涉及巴比妥类药物名称混淆(例如,在检测订单或医生记录中戊巴比妥和苯巴比妥混淆),这似乎对TDM有效性影响最小,戊巴比妥血清/血浆浓度通常在目标范围内。实验室自行开发的戊巴比妥免疫测定法显示与苯巴比妥和布他比妥有交叉反应,通过碱性和加热预处理可消除这种交叉反应。该免疫测定法在20 mcg/mL范围内呈线性,并且与参考实验室的气相色谱 - 质谱测量结果密切相关。

结论

戊巴比妥TDM可通过在自动化临床化学平台上进行免疫测定来完成,为基于色谱的方法提供了一种替代方法。巴比妥类药物名称混淆很常见,尤其是戊巴比妥和苯巴比妥。

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