PMID- 34247386
OWN - NLM
STAT- MEDLINE
DCOM- 20220301
LR  - 20220301
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 62
IP  - 9
DP  - 2021 Sep
TI  - Levetiracetam dosing in patients receiving continuous renal replacement therapy.
PG  - 2151-2158
LID - 10.1111/epi.16971 [doi]
AB  - OBJECTIVE: 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). METHODS: 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 x 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. RESULTS: 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. 
      SIGNIFICANCE: 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.
CI  - (c) 2021 International League Against Epilepsy.
FAU - Chaijamorn, Weerachai
AU  - Chaijamorn W
AD  - Faculty of Pharmacy, Siam University, Bangkok, Thailand.
FAU - Charoensareerat, Taniya
AU  - Charoensareerat T
AD  - Faculty of Pharmacy, Siam University, Bangkok, Thailand.
FAU - Rungkitwattanakul, Dhakrit
AU  - Rungkitwattanakul D
AD  - Department of Clinical and Administrative Pharmacy Sciences, College of Pharmacy, 
      Howard University, Washington, DC, USA.
FAU - Phunpon, Sathian
AU  - Phunpon S
AD  - Faculty of Pharmacy, Siam University, Bangkok, Thailand.
FAU - Sathienluckana, Thanompong
AU  - Sathienluckana T
AD  - Faculty of Pharmacy, Siam University, Bangkok, Thailand.
FAU - Srisawat, Nattachai
AU  - Srisawat N
AD  - Division of Nephrology, Department of Medicine, Faculty of Medicine, 
      Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Bangkok, 
      Thailand.
AD  - Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial 
      Hospital, Bangkok, Thailand.
AD  - Critical Care Nephrology Research Unit, Faculty of Medicine, Chulalongkorn 
      University, Bangkok, Thailand.
AD  - Academic of Science, Royal Society of Thailand, Bangkok, Thailand.
AD  - Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand.
AD  - Department of Critical Care Medicine, Center for Critical Care Nephrology, The 
      CRISMA Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
FAU - Pattharachayakul, Sutthiporn
AU  - Pattharachayakul S
AUID- ORCID: 0000-0002-2879-2105
AD  - Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of 
      Songkla University, Songkhla, Thailand.
LA  - eng
PT  - Journal Article
DEP - 20210711
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anti-Bacterial Agents)
RN  - 44YRR34555 (Levetiracetam)
SB  - IM
MH  - Anti-Bacterial Agents/therapeutic use
MH  - *Continuous Renal Replacement Therapy
MH  - Critical Illness
MH  - Humans
MH  - Levetiracetam
MH  - Monte Carlo Method
OTO - NOTNLM
OT  - continuous renal replacement therapy
OT  - critically ill patients
OT  - drug dosing
OT  - levetiracetam
OT  - pharmacokinetics
EDAT- 2021/07/12 06:00
MHDA- 2022/03/03 06:00
CRDT- 2021/07/11 21:02
PHST- 2021/06/02 00:00 [revised]
PHST- 2021/05/16 00:00 [received]
PHST- 2021/06/04 00:00 [accepted]
PHST- 2021/07/12 06:00 [pubmed]
PHST- 2022/03/03 06:00 [medline]
PHST- 2021/07/11 21:02 [entrez]
AID - 10.1111/epi.16971 [doi]
PST - ppublish
SO  - Epilepsia. 2021 Sep;62(9):2151-2158. doi: 10.1111/epi.16971. Epub 2021 Jul 11.