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ArticleNaunyn-Schmiedeberg's archives of pharmacology2025

Population pharmacokinetics of levetiracetam in Chinese adult epilepsy patients with varying renal function: exposure simulation and individualized dosing adjustments.

Rongrong Wang, Ze Li, Shu Li, Yaoyu Zhang, Le Cai, Tinglin Ren, Rongyan Li, Xingang Li, Tianlin Wang

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In one paragraph

Article in Naunyn-Schmiedeberg's archives of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Rongrong WangDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China.
Ze LiDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, China.
Shu LiDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China.
Yaoyu ZhangDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China.
Le CaiDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China.
Tinglin RenDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China.
Rongyan LiDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China.
Xingang LiDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, China. lxg198320022003@163.com.
Tianlin WangDepartment of Pharmacy, Medical Supplies Center, Chinese PLA General Hospital, Haidian District, No. 28 Fuxing Road, Beijing, 100853, China. wangtl_301@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Levetiracetam (LEV) has become a first-line treatment option for various types of epilepsy with a broad spectrum of efficacy and favorable pharmacokinetic profile. We aimed to develop a population pharmacokinetic (PPK) model for LEV and devise a model-based dosing guideline specific to Chinese adult epilepsy patients. Employing Phoenix NLME 7.0 software, we utilized the first-order conditional estimation and extended least squares method to establish the PPK model. The PK of LEV was effectively characterized using a one-compartment model. Monte Carlo simulations were then performed to generate dosing guidelines suitable for various patient groups. The Bayesian feedback method was employed to develop the clinical individual predictive model. Data from 80 Chinese adult patients yielded 148 LEV plasma concentrations for analysis. In the final model, the absorption rate constant was fixed at 2.44. The apparent volume of distribution and the apparent clearance (CL/F) had population typical values of 35.34 L and 3.24 L/h, respectively. CL/F of LEV was significantly influenced by creatinine clearance (CrCL), identified as a major covariate. Monte Carlo simulations indicated that regimens of 0.5 g, 0.75 g, 1.0 g, 1.5 g, 2.0 g, 2.5 g, and 3.5 g twice daily were associated with the highest probability of target attainment (PTA) in patients with different renal function levels. Accordingly, a user-friendly dose recommendation was formulated for these patients. The individual predictive model accurately matched the observed concentrations and managed to guide the personalized dose adjustment. The PPK model linked CL/F to CrCL. Model-based simulations suggest that higher dosage adjustments may be necessary for those with augmented renal function. The developed clinical individual predictive model could effectively guide personalized dose adjustments, potentially reducing the need for frequent drug concentration measurements.

Indexed as

AnticonvulsantsEpilepsyKidneyLevetiracetamModels, BiologicalAdolescentAdultBayes TheoremComputer SimulationDose-Response Relationship, DrugEast Asian PeopleFemaleHumansMaleMiddle AgedMonte Carlo MethodAnticonvulsantsLevetiracetamAugmented renal functionCreatinine clearanceEpilepsyIndividual predictionLevetiracetamPopulation pharmacokinetics

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.