Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 50, 2020 - Issue 9
347
Views
6
CrossRef citations to date
0
Altmetric
Clinical Pharmacokinetics and Metabolism

Pharmacokinetic and pharmacodynamic modeling of levetiracetam: investigation of factors affecting the clinical outcome

ORCID Icon, , , , , , , & ORCID Icon show all
Pages 1090-1100 | Received 06 Feb 2020, Accepted 21 Mar 2020, Published online: 07 Apr 2020
 

Abstract

  1. This study aimed to evaluate the pharmacokinetics and pharmacodynamics of oral levetiracetam therapy in drug refractory adult epileptic outpatients, as well as factors affecting them. Concentration–time data were collected at steady state, while seizure recurrence was monitored for 13 months. Non-linear mixed effects modeling was applied, and covariates assessed included weight, height, age, daily dose and creatinine clearance.

  2. Plasma concentrations of levetiracetam were best described by a one-compartment pharmacokinetic model (V/F = 34.7 L) with first-order absorption (ka = 0.616 h−1) and clearance (CL/F = 3.26 L/h). Patient’s CrCL was found to significantly affect levetiracetam clearance (beta = 0.795). Time to seizure occurrence followed an exponential distribution and the mean time to seizure occurrence was estimated Te = 22.08 days. Seizure rate per month followed a Poisson distribution, while mean seizure rate per month was estimated λ = 1.33. Daily dose significantly affected the mean estimated time to seizure (beta = −2.2) and the mean monthly seizure rate (beta = 2.27) in a reverse way. Using discrete time Markov chains, it was shown that the transition probability from focal seizures to focal to bilateral tonic-clonic is significantly altered in relation to patient’s CrCL.

  3. Simulations showed that dose should be adjusted in relation to CrCL, while low doses of levetiracetam are more effective for seizure control. Modeling and simulation in every-day clinical practice may provide significant information for the optimization of seizure control using well-known agents.

Disclosure statement

The authors report no declarations of interest.

Data availability statement

The data that support the findings of this study are available upon request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 897.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.