Chapter 19 - Individualizing Antiepileptic Therapy for Patients

Abstract

Therapeutic drug monitoring (TDM) is a part of personalized medicine. Even if there is no evidence from randomized trials, the clinical value of thoughtfully and appropriately used TDM for so-called older antiepileptic drugs (AEDs) (eg, phenytoin, valproates, carbamazepine, and phenobarbital) is well established in clinical practice. A position paper by the subcommission on TDM, International League Against Epilepsy Commission on Therapeutic Strategies, in 2008 suggested new definitions, and the concept of “an individual therapeutic concentration,” not a general reference range, was recommended. This chapter summarizes the lengthy experience with TDM, population pharmacokinetics (PK) modeling, and individualizing dosage regimens of older AEDs given as monotherapy and polytherapy. Anticonvulsant monitoring of adult and pediatric patients have been routinely collected in PK services in Russia since the 1990s and analyzed retrospectively. The relatively rich TDM data (peak–trough sampling strategy, repeated measurements over 1- to 6-year periods in some patients) make it possible not only to develop simple linear and more complex nonlinear population PK models for individualizing dosage regimens, but also to evaluate how well this method works in real clinical settings. For TDM of AEDs, future developments include AED measurement in saliva and other less invasive methods. Portable near-patient testing devices, minimally invasive, simple, and low-cost methods for online TDM enable wider and more effective implementation of TDM. Continuous sampling may permit more complex PK models for drugs or drug combinations to be identified from such “rich” TDM data and used for dosage individualization. More intensive TDM procedures open a possibility for investigation of relationship between PK and pharmacodynamic measures as well as PK/PD modeling of AEDs.