Therapeutic drug monitoring of levetiracetam in newborns
- Authors: Bondareva I.B.1, Ivzhits M.A.1,2, Zyryanov S.K.1,2, Chenkurov M.S.1
-
Affiliations:
- Peoples' Friendship University of Russia
- City Clinical Hospital No.24
- Issue: Vol 13, No 4 (2019)
- Pages: 65-76
- Section: Reviews
- Submitted: 26.12.2019
- Published: 26.12.2019
- URL: https://annaly-nevrologii.com/journal/pathID/article/view/621
- DOI: https://doi.org/10.25692/ACEN.2019.4.9
- ID: 621
Cite item
Full Text
Abstract
Neonatal seizures in full-term and preterm infants represent a common neurological syndrome. Levetiracetam (LEV) is one of the new and widely prescribed second- or third-line antiepileptic drug for the treatment of seizures. Routine therapeutic drug monitoring of LEV was not recommended due to its almost ideal pharmacokinetic profile: linear pharmacokinetics, predictable dose-concentration relationship, wide therapeutic index, favourable safety profile, and unlikely clinically significant drug-drug pharmacokinetic interactions.
In newborns, drug pharmacokinetics may be under the influence of maturation process. LEV pharmacokinetics in newborns appears to be age (gestational, postnatal) dependent and highly variable within the age ranges. These aspects make therapeutic drug monitoring a useful procedure for therapy optimization in this specific patient population.
In population modeling based on therapeutic drug monitoring and nonlinear mixed effects models, covariates were found that should significantly affect the LEV clearance and volume of distribution in newborns — creatinine clearance and total body weight. Using of these regression equations can help to adjust the LEV doses without the patient's measured concentration data. But the significant magnitudes of the interindividual variability remaining in these final regression models justify the need for therapeutic drug monitoring and Bayesian adaptive control for personalization of LEV dosage regimens in neonates.
About the authors
Irina B. Bondareva
Peoples' Friendship University of Russia
Author for correspondence.
Email: i_bomdareva@yahoo.com
Russian Federation, Moscow
Marina A. Ivzhits
Peoples' Friendship University of Russia; City Clinical Hospital No.24
Email: i_bomdareva@yahoo.com
Russian Federation, Moscow
Sergey K. Zyryanov
Peoples' Friendship University of Russia; City Clinical Hospital No.24
Email: i_bomdareva@yahoo.com
Russian Federation, Moscow
Mikhail S. Chenkurov
Peoples' Friendship University of Russia
Email: i_bomdareva@yahoo.com
Russian Federation, Moscow
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