Abstract: FR-PO226
Ceftazidime Dosing Recommendations in Patients Receiving Various Home Hemodialysis Regimens
Session Information
- Pharmacology
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)
- 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)
Authors
- Lewis, Susan J., University of Findlay College of Pharmacy, Findlay, Ohio, United States
- Jang, Soo min, Loma Linda University, Loma Linda, California, United States
- Mueller, Bruce A., University of Michigan College of Pharmacy, Ann Arbor, Michigan, United States
Background
Home hemodialysis (HHD) regimens differ from those for typical in-center thrice-weekly hemodialysis in frequency, duration and dialysate volume. In recent years, HHD is increasingly used, but the literature for drug dosing in HHD is sparse. This study was aimed to determine optimal ceftazidime dosing regimens in end stage kidney disease patients with various HHD regimens using Monte Carlo simulation (MCS) techniques.
Methods
Pharmacokinetic models were constructed using internal outpatient dialysis patient demographic information and pertinent pharmacokinetic data to predict ceftazidime plasma concentrations in 5,000 virtual patients receiving HHD. MCS was performed to assess the probability of target attainment (PTA) of various ceftazidime doses in 10 different HHD settings (Table). All ceftazidime doses were simulated to be infused post-dialysis. The efficacy target was free serum ceftazidime concentrations above 4 times the minimum inhibitory concentration for at least 60% of the dosing interval (fT>4xMIC; MIC=8 mg/L for Pseudomonas aeruginosa). The smallest doses attaining PTA≥90% of virtual patients during 1-week of therapy were considered optimal to minimize toxicity concerns. The assumption was made that ceftazidime therapeutic drug monitoring services were unavailable.
Results
The lowest ceftazidime doses that met PTA goals in >90% of virtual patients for ten different HHD regimens are shown in the figure. Required ceftazidime doses differed depending on interdialytic-period (e.g. 1-3 days) and the prescribed dialysate volumes.
Conclusion
MCS predicted that HHD patients would require different ceftazidime doses from those recommended for typical thrice-weekly hemodialysis to ensure PTA in >90% of virtual patients. Further clinical validation of these findings is necessary.
Ceftazidime doses that met pharmacodynamic targets in 90% of virtual patients in ten HHD regimens.
Funding
- Commercial Support – Fresenius