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.

Background: Rivaroxaban is an oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier to maximise the benefit of the medications. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. Methods: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence. Results: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6-20 h. A missed dose should be skipped if less than 4 h remains before the next dose. Age or renal function does not significantly influence remedial dosing regimens. The proposed regimens resulted in shorter deviation time than that of the EHRA guide in most non-adherence scenarios. Conclusion: EHRA guide may not provide optimal remedial strategies for rivaroxaban-treated non-adherent patients based on simulation. PK/PD and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban for patients with NVAF, which could help to minimise the risk of bleeding and thromboembolism.