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重复给予利培酮、帕利哌酮、喹硫平、奥氮平或阿立哌唑后毛细血管和静脉血浆药物浓度的比较。

Comparison of Capillary and Venous Plasma Drug Concentrations After Repeated Administration of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole.

机构信息

Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.

Janssen Research & Development, LLC, Raritan, NJ, USA.

出版信息

Clin Pharmacol Drug Dev. 2016 Nov;5(6):538-547. doi: 10.1002/cpdd.291. Epub 2016 Aug 17.

Abstract

Quantification of blood levels of antipsychotic drugs may be useful for managing medication therapy. This open-label, parallel-group study was performed to compare finger-stick-based capillary with corresponding venous plasma concentrations for risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole and their major metabolites after repeated dosing in patients with schizophrenia or related illnesses. Finger-stick-based capillary and venous blood samples were collected at various times within a dosing interval. All drug concentration measurements in the derived plasma samples were performed with validated liquid chromatography-tandem mass spectrometry methods. Finger-stick-based capillary and venous plasma drug concentrations after repeated dosing were generally similar. Olanzapine capillary plasma concentrations, however, were on average approximately 20% higher than venous concentrations, with a trend for a relatively greater difference occurring shortly after dosing. In addition, smaller capillary-venous differences were observed for extended-release and long-acting intramuscular formulations and for aripiprazole, a drug with a long half-life, compared with drugs administered as an immediate-release formulation (risperidone, olanzapine). After repeated dosing, plasma derived from finger-stick-based blood was observed to be predictive of the venous concentrations. Capillary sampling may be an appropriate alternative to venous sampling to readily evaluate systemic drug concentrations.

摘要

定量检测抗精神病药物的血药浓度可能有助于管理药物治疗。本开放性、平行组研究旨在比较精神分裂症或相关疾病患者重复给药后基于指尖采血的毛细血管与相应静脉血浆中利培酮、帕利哌酮、喹硫平、奥氮平和阿立哌唑及其主要代谢物的浓度。在给药间隔内的不同时间采集基于指尖采血的毛细血管和静脉血样。所有衍生血浆样本中的药物浓度测量均采用经过验证的液相色谱-串联质谱法进行。重复给药后的基于指尖采血的毛细血管和静脉血浆药物浓度通常相似。然而,奥氮平毛细血管血浆浓度平均比静脉浓度高约 20%,并且在给药后不久,这种差异相对较大的趋势更为明显。此外,与作为速释制剂给药的药物(利培酮、奥氮平)相比,对于延长释放和长效肌内制剂以及半衰期较长的阿立哌唑,观察到毛细管-静脉差异较小。重复给药后,基于指尖采血的血液衍生的血浆被观察到可预测静脉浓度。与静脉采血相比,毛细管采血可能是一种评估系统药物浓度的合适替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfa9/5132144/246f60a778c2/CPDD-5-538-g001.jpg

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