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

Abstract

The primary cause of the variability of Cf in pharmacology is the change in plasma protein binding (PPB), thus PPB monitoring should be applied to a better individualization of drug dosage regimens in clinical patients.

An elderly case of consciousness disturbance due to levetiracetam and low doses of carbamazepine

“…Unlike LEV treatment protocols, CBZ drug monitoring methods are well established, and there is a strong correlation between the blood concentration and clinical adverse effects of CBZ [3]. A blood concentration of 4-12 µg/mL can safely prevent epilepsy [2]. However, in elderly people, if the CBZ blood concentration exceeds 8 μg/mL, neurological adverse effects such as ataxia, nystagmus, convulsions, and coma are likely to occur [8].…”

“…Hypoalbuminemia increases the concentration of CBZ in the cerebrospinal fluid (Cf-CBZ) despite a low blood concentration and causes adverse effects of central nervous system disorders. Because CBZ is largely bound to albumin, hypoalbuminemia increases free CBZ in the blood [2]. It has been shown that Cf-CBZ increases as the amount of free CBZ in the blood increases [9].…”

“…In patients with epilepsy, consciousness disturbances may occur due to seizures or adverse effects of the prescribed antiepileptic drugs, making it challenging to distinguish the underlying causes of these disturbances. Two antiepileptic drugs, levetiracetam (LEV) and carbamazepine (CBZ), are widely used because they have fewer adverse effects including consciousness disturbance [1][2][3]. However, disturbances still occur in certain patients treated with these drugs.…”

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

“…These results suggested that accuracy measurement of free VPA using traditional UF pre-treatment was dependent on albumin concentration; therefore, the authors recommend that the HFCF-UF should be the method of choice for the TDM of plasma free VPA [ 68 ]. In another work, Gao and coworkers applied HFCF-UF coupled to HPLC to quantify free CBZ in clinical samples [ 69 ]. The main advantage of this procedure was the possibility of evaluating both free and total concentrations from the same plasma sample.…”

“…The authors reported high recovery and reproducibility and no significant NSA. The method developed was successfully applied in the TDM of 20 epileptic patients undergoing CBZ therapy, but further studies on a larger number of patients are undoubtedly required to fully evaluate the potential of this approach [ 69 ].…”