Aim This is the first review to summarize the population pharmacokinetic studies of oxcarbazepine and explored the significant covariates that may have an impact on the dosage regimen and clinical use of oxcarbazepine. Methods PubMed and Embase databases were searched before 31 October 2020, and references of all selected studies were further screened to identify the pertinent population pharmacokinetic studies of oxcarbazepine. Relevant information about the identified population pharmacokinetic studies was summarised, and the quality of the reports was evaluated. Moreover, studies among infant, children, and adult patients were compared. Results Twelve studies were included: seven studies enrolled paediatric patients only; two enrolled both paediatric and adult patients; and two enrolled adult patients only. The apparent clearance per weight for children (median: 0.0505 L/h/kg, range: 0.016-0.084) and infants (0.078 L/h/kg) were higher than that for adults (median: 0.036 L/h/kg, range: 0.029-0.06). Furthermore, children had a larger variation on clearance compared to adults. Weight, co-administration with enzyme-inducing antiepileptic drugs, and renal function were found to significantly affect clearance of 10-hydroxycarbazepine. Conclusion The oxcarbazepine dose regimen was dependent on weight, co-administration with enzyme-inducing medications, and renal function. Further study is essential to explore the pharmacodynamics in epilepsy patients and pharmacokinetics of oxcarbazepine in infants.

Aim: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for long-term stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOACs is unsatisfactory and decreases over time. The aim of this study was to explore appropriated remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through the Monte Carlo simulation. Methods: Six proposed regimens were compared with the recommendations in the European Heart Rhythm Association (EHRA) guide regarding the trough total deviation time considering both edoxaban plasma concentration and inactive factor Xa activity. Monte Carlo simulations were performed using RxODE based on the published population pharmacokinetics/pharmacodynamics model. Results: The proposed remedial strategies were different from EHRA recommendations and were related to delay duration. The missed dose can be taken immediately if the delay time is within 11 h. When the delay period is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred compared to that recommended in the EHRA guide. Our proposed strategies resulted in a shorter total deviation time than EHRA guide. Conclusion: PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which could help maximize its therapeutic effect.