Levetiracetam dosing in patients receiving continuous renal replacement therapy.
continuous renal replacement therapy
critically ill patients
drug dosing
levetiracetam
pharmacokinetics
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
02
06
2021
received:
16
05
2021
accepted:
04
06
2021
pubmed:
12
7
2021
medline:
3
3
2022
entrez:
11
7
2021
Statut:
ppublish
Résumé
The study was aimed to define appropriate levetiracetam dosing regimens from available published pharmacokinetics (PK) studies in critically ill patients with and without cirrhosis receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulation (MCS). Mathematical pharmacokinetic models were developed using published demographic and PK data in adult critically ill patients with known variability and correlations between PK parameters. CRRT modalities (continuous venovenous hemofiltration and continuous venovenous hemodialysis) with different effluent rates were modeled. Levetiracetam regimens from available clinical resources were evaluated on the probability of target attainment (PTA) using pharmacodynamics (PD) target of the trough concentrations and area under the time-concentration curve within a range of 6-20 mg/L and 222-666 mg × hour/L for the initial 72 hours of therapy, respectively. Optimal regimens were defined from regimens that yielded the highest PTA. Each regimen was tested in a group of different 10,000 virtual patients. Our results showed the optimal levetiracetam dosing regimen of 750-1000 mg every 12 hours is recommended for adult patients receiving both CRRT modalities with two different effluent rates of 25 and 35 mL/kg/h. Child-Pugh class C cirrhotic patients undergoing CRRT required lower dosing regimens of 500-750 mg every 12 ours due to smaller non-renal clearance. Of interest, some of literature-based dosing regimens were not able to attain the PK and PD targets. Volume of distribution, non-renal clearance, CRRT clearance, and body weight were significantly correlated with the PTA targets. Dosing adaptation in this vulnerable population should be concerned. Clinical validation of our finding is absolutely needed.
Substances chimiques
Anti-Bacterial Agents
0
Levetiracetam
44YRR34555
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2151-2158Informations de copyright
© 2021 International League Against Epilepsy.
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