The significance of a new parameter - plasma protein binding - in therapeutic drug monitoring and its application to carbamazepine in epileptic patients

作者：Gao, Jing-lin; Wang, Xin-yu; An, Jing; Du, Chao-hui; Li, Meng-jiao; Ma, Hai-yan; Zhang, Li-na; Bian, Jing; Jiang, Ye^*

来源：RSC Advances, 2017, 7(45): 28048-28055.

DOI：10.1039/c7ra02991h

• PERFORMANCE LIQUID-CHROMATOGRAPHY
• MULTIPLIED IMMUNOASSAY TECHNIQUE
• TANDEM MASS-SPECTROMETRY
• ULTRAFILTRATION
• QUANTIFICATION
• VALIDATION
• METABOLITE
• ACCURACY

Free drug concentration (C-f) is instantaneous and susceptible to sampling time, which can confuse clinicians and cause them to adjust the dosage regimen. In the present work, we indicated a new parameter, the plasma protein binding (PPB) of clinical plasma samples, and discussed its application in TDM (Therapeutic Drug Monitoring). Furthermore, carbamazepine was selected as a model drug to develop a simple pretreatment method for the determination of PPB, in which C-f and C-t can be simultaneously analyzed in one plasma sample using a single device. Our results demonstrated that this proposed method exhibited some advantages, including perfect recovery (approximately 100%) and high precision (CV% < 3.0%). Furthermore, it achieved successful application in real plasma samples. Individual differences in PPB (from 10.1-68.9%) were among patients, and in additon, between the patients and healthy people (p < 0.05). Moreover, there was a weak correlation between C-t and C-f (r(2) = 0.470 and p < 0.05), so the C-f of CBZ cannot be estimated from C-t. However, the primary cause of the variability of C-f is the change in PPB. As a consequence, applying PPB to guide individual dose adjustment is more accurate and more scientific than using C-f or C-t.

• 出版日期2017
• 单位河北省人民医院; 河北医科大学