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

Abstract

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 (r² = 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.