Abstract: SA-PO651

Personalized Levetiracetam Dosing Adjustments for Patients Undergoing Continuous Venovenous Hemofiltration

Session Information

Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

  • 1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics

Authors

  • Kalaria, Shamir, University of Maryland, Baltimore, Maryland, United States
  • Mccarthy, Paul J., University of Maryland, Baltimore, Maryland, United States
  • Franquiz, Miguel, University of Maryland, Baltimore, Maryland, United States
  • Armahizer, Michael, University of Maryland Medical Center, Baltiomre, Maryland, United States
  • Gopalakrishnan, Mathangi, School of Pharmacy, University of Maryland, Baltimore, Baltimore, Maryland, United States
Background

Few clinical data exist on the effect of continuous renal replacement therapy (CRRT) methods on medication pharmacokinetics (PK). Appropriately designed PK studies could potentially optimize dosing recommendations in patients undergoing CRRT. This clinical study in critically ill patients receiving levetiracetam aims to understand the (1) methodology of conducting an appropriate CRRT study to characterize PK, (2) potential barriers that exist with an observational CRRT study, and (3) derivation of individualized dosing recommendations.

Methods

Five patients receiving oral or intravenous levetiracetam and continuous venovenous hemofiltration (CVVH) in a neurocritical care unit were sampled to investigate the need for dosing adjustments. Pre-filter, post-filter, and ultrafiltrate samples were taken before dosing, after the completion of a 15 minute infusion, and at 4-5 additional time points post-infusion. Plasma concentrations were determined using a validated HPLC-UV bioanalytical method. Blood and effluent flow rates and laboratory parameters were also collected at the time of sampling. Non-compartmental analysis was conducted using Phoenix WinNonlin® 7.1 (Pharsight Corporation).

Results

The average sieving coefficient (ratio of ultrafiltrate concentrations to prefilter plasma concentrations) was 0.90 ± 0.1 and the average volume of distribution was 52.7 ± 7.6 liters. Three out of the five patients experienced concentrations outside the reported therapeutic range (12-46 mg/L) of levetiracetam. Average total drug clearance for patients taking 750 mg, 1000 mg, and 2000 mg were 3.10, 5.14, and 3.46 L/hr respectively, indicating that differences in clearance can be attributed to differences in ultrafiltration flow rates.

Conclusion

Preset ultrafiltrate rates were different amongst patients and need to be taken into consideration when determining an appropriate dose. Patients with higher ultrafiltrate rates will have increased drug clearance and therefore will require higher doses in order to match exposures seen in patients with normal renal function. Therefore, individualized dosing recommendations should be based on CRRT flow parameters and drug specific sieving coefficients.

Funding

  • Private Foundation Support