Methods: Adult patients hospitalized at an academic medical center receiving HD and TZP were prospectively enrolled after informed consent. Demographic data, TZP indication, and steady state serum PIP concentrations were collected. After 72 hrs of therapy, blood samples were drawn before a dose and then 30 min, 1, 2, 4, and 8 hrs after the start of the infusion on a non-HD day. Samples were also collected prior to starting HD and then again 1 hr after completion. PIP concentrations were determined using a validated HPLC assay. PK parameters were derived for each patient using non-compartmental analysis. A 10,000 subject Monte Carlo Simulation was performed using Crystal Ball® to determine the probability of target attainment (PTA) of 50%fT>MIC at MICs ranging from 1-64 mg/L.
Results: 10 patients [8 men, 2 women; median (range) age, 61 (31-85) years] with a variety of infections receiving TZP 2.25g q 8hrs were enrolled. The median half-life and AUCt(0-8) was 6.89 (1.8-13.75) hrs and 567.55 (268.92-1289.59) mg*hr/L, respectively. Steady-state volume of distribution was 0.32 (0.12-0.46) L/kg and clearance was 0.4 (0.2-0.7) L/hr/kg. After receiving HD, the half-life was 1.94 (1.02-3.15) hrs resulting in a median 24% (10.03-59.88) drug removal. A 30 min bolus of PIP 2g q 8hrs achieved a PTA of 95% for MICs < 16 mg/L. The PTA for MICs 32 mg/L and 64 mg/L were 35% and 1% respectively.
Conclusion: The PK of PIP in HD patients exhibited a prolonged half-life and increased AUC. The current FDA approved dosing regimen of TZP for HD patients achieves adequate drug concentrations to maximize its PK/PD target of at least 50%fT>MIC against organisms with a MIC < 16 mg/L.
D. J. Feola, None
C. A. Martin, None
D. S. Burgess, None