Case Report: Predicting the Range of Lamotrigine Concentration Using Pharmacokinetic Models Based on Monte Carlo Simulation: A Case Study of Antiepileptic Drug-Related Leukopenia

Abstract

Lamotrigine (LTG), a wide-spectrum antiepileptic drug, is frequently associated with cutaneous side-effects, whereas hematological side-effects such as leukopenia have rarely been reported for it. We report the case of a 15-year-old Chinese female epileptic patient weighing 60 kg who developed combined asymptomatic leukopenia after receiving concomitant therapy with LTG and valproate acid (VPA). In this case report, antiepileptic drug-related leukopenia may have occurred in definite relation to an increase in LTG concentration and reversed with the discontinuation of VPA. Monte Carlo (MC) simulations were performed to estimate the steady-state serum concentrations (Css) of LTG for different dosing regimens in adolescent Chinese epileptic patients weighing the same as the patient considered in the case study, based on pharmacokinetic (PK) models published in past research. Adjustments to the dosage of LTG for the patient were analyzed to illustrate the application of MC simulations and verify the results. The predicted LTG concentrations within a prediction interval between the 10th and 90th percentiles that represented 80% of the simulated populations, could adequately capture the measured LTG concentrations of the patient, indicating that MC simulations are a useful tool for estimating drug concentrations. Clinicians may benefit from the timely probabilistic predictions of the range of drug concentration based on an MC simulation that considers a large sample of virtual patients. The case considered here highlights the importance of therapeutic drug monitoring (TDM) and implementing model-informed precision dosing in the course of a patient’s individualized treatment to minimize adverse reactions.