Population Pharmacokinetics of Levetiracetam: a Systematic Review

Author:

Methaneethorn Janthima1ORCID,Leelakanok Nattawut2ORCID

Affiliation:

1. Pharmacokinetic Research Unit, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

2. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand

Abstract

Background: The use of levetiracetam (LEV) has been increasing given its favorable pharmacokinetic profile. Numerous population pharmacokinetic studies for LEV have been conducted. However, there are some discrepancies regarding factors affecting its pharmacokinetic variability. Therefore, this systematic review aimed to summarize significant predictors for LEV pharmacokinetics as well as the need for dosage adjustments. Methods: We performed a systematic search for population pharmacokinetic studies of LEV conducted using a nonlinear-mixed effect approach from PubMed, Scopus, CINAHL Complete, and Science Direct databases from their inception to March 2020. Information on study design, model methodologies, significant covariate-parameter relationships, and model evaluation was extracted. The quality of the reported studies was also assessed. Results: A total of 16 studies were included in this review. Only two studies were conducted with a two-compartment model, while the rest were performed with a one-compartment structure. Bodyweight and creatinine clearance were the two most frequently identified covariates on LEV clearance (CLLEV). Additionally, postmenstrual age (PMA) or postnatal age (PNA) were significant predictors for CLLEV in neonates. Only three studies externally validated the models. Two studies conducted pharmacodynamic models for LEV with relatively small sample size. Conclusion: Significant predictors for LEV pharmacokinetics are highlighted in this review. For future research, a population pharmacokinetic-pharmacodynamic model using a larger sample size should be conducted. From a clinical perspective, the published models should be externally evaluated before clinical implementation.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmacology (medical),General Pharmacology, Toxicology and Pharmaceutics,General Medicine

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