Steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients

作者：Cheatham S Christian; Shea Katherine M; Healy Daniel P; Humphrey Melissa L; Fleming Megan R; Wack Matthew F; Smith David W; Sowinski Kevin M; Kays Michael B^*

来源：International Journal of Antimicrobial Agents, 2011, 37(1): 46-50.

DOI：10.1016/j.ijantimicag.2010.08.016

• Cefepime
• Pharmacokinetics
• Pharmacodynamics
• Monte Carlo

The objective of this study was to evaluate the steady-state pharmacokinetics and pharmacodynamics of cefepime administered by prolonged infusion in hospitalised patients requiring antimicrobial therapy. Nine patients received 1 g every 8 h (q8h), infused over 4 h, and steady-state pharmacokinetic parameters were determined by non-compartmental and compartmental methods. Using these pharmacokinetic parameters, 5000-patient Monte Carlo simulations were performed to estimate the pharmacokinetic profiles for six prolonged-infusion dosing regimens. The probability of target attainment (PTA) was calculated at minimum inhibitory concentrations (MICs) ranging from 0.06 mu g/mL to 32 mu g/mL, and the cumulative fraction of response (CFR) was calculated for six Gram-negative pathogens using MIC data from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) (2005-2007, USA). The pharmacodynamic target was free cefepime concentrations remaining above the MIC for 60% of the dosing interval (60% fT > MIC). Mean +/- standard deviation maximum and minimum serum concentrations, terminal elimination half-life, elimination rate constant, volume of distribution and systemic clearance of cefepime were 32.5 +/- 13.5 mu g/mL, 9.5 +/- 5.2 mu g/mL, 2.4 +/- 0.7 h, 0.316 +/- 0.116 h(-1), 21.3 +/- 6.5 L and 6.6 +/- 3.6 L/h, respectively. At the susceptibility breakpoint of 8 mu g/mL, the PTA was > 90% for 1 g and 2 g q8h (4-h infusion) and 1 g and 2 g every 6 h (q6h) (3-h infusion). For Pseudomonas aeruginosa, the CFR was 88.6% for 1 g q8h (4-h infusion) and >= 92.7% for 2 g q8h (4-h infusion) and 1 g and 2 g q6h (3-h infusion). Cefepime 1 g q8h infused over 4 h provides excellent target attainment for susceptible bacterial pathogens with MICs <= 8 mu g/mL.

• 出版日期2011-1