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

Free drug concentration (Cf) 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 Cf and Ct 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 Ct and Cf (r2 = 0.470 and p < 0.05), so the Cf of CBZ cannot be estimated from Ct. However, the primary cause of the variability of Cf is the change in PPB. As a consequence, applying PPB to guide individual dose adjustment is more accurate and more scientific than using Cf or Ct.