Physiologically based pharmacokinetic model for oxcarbazepine active metabolite to predict pharmacokinetics in paediatric patients with renal impairment and adjust dosages.

IF 3.1 3区医学 Q2 PHARMACOLOGY & PHARMACY

British journal of clinical pharmacology Pub Date : 2025-02-17 DOI:10.1002/bcp.70016

Cheng-Jie Ke, Si-Ting Liu, Yu-Die Qian, Xiang You, Rong-Fang Lin, Cui-Hong Lin, Pin-Fang Huang, Wei-Wei Lin

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引用次数: 0

Abstract

Aims: Oxcarbazepine (OXC) has been approved as monotherapy or adjunctive therapy for paediatric partial seizures. There are few reports on the pharmacokinetics (PK) of OXC in paediatric patients with renal impairment (RI), especially dosage studies of RI, which are rarely conducted on paediatric patients. This study aimed to predict the PK of OXC in children with RI and to provide recommendations for dose adjustment in this population.

Methods: Physiologically based pharmacokinetic (PBPK) models of the active metabolites of OXC were developed and verified, and their disposition was simulated in populations with or without RI.

Results: A fold error value of less than 2 was observed based on the simulated results from PBPK models for single- and multi-dose administration. Based on the predictions for paediatric patients with moderate, severe, and end-stage RI, the dose should be adjusted to 50, 40 and 25% of the normal dose, respectively, in children aged 2-5 years; and 50, 30 and 20%, respectively, in children aged 6-17 years.

Conclusions: The developed PBPK model is a valuable tool for predicting the OXC dosage in paediatric patients with RI.

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来源期刊

British journal of clinical pharmacology 医学-药学

CiteScore

6.30

自引率

8.80%

发文量

419

审稿时长

1 months

期刊介绍： Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.