Cefazolin pharmacokinetics (PK) in obesity are limited to single dose administration for surgical prophylaxis. The objectives of this study were to evaluate the steady-state PK and pharmacodynamics (PD) of cefazolin in infected non-obese and obese patients and to evaluate probability of target attainment (PTA) at specific MICs.
Hospitalized patients requiring treatment with cefazolin for a suspected or documented bacterial infection were enrolled. Patients weighting < 120 kg (Group 1) received 2 grams q8h, and patients weighing > 120 kg (Group 2) received 3 grams q8h. Doses were infused over 0.5 h, and serial blood samples were collected after 4 or more doses. Protein binding was determined by ultrafiltration, and total and unbound (free) serum concentrations were determined by HPLC. PK parameters were estimated, and 5,000-patient Monte Carlo simulations were performed using the PK parameters for the free concentrations to calculate PTA at specific MICs using the PD targets of 40% and 60% fT>MIC.
Twenty-two patients (11 in each group) were studied. Patient demographics for Group 1 vs. Group 2 were (mean ± SD): age, 62 ± 11 years vs. 53 ± 11 years; total body weight, 87.2 ±15.4 kg vs. 174.5 ± 69.6 kg; body mass index, 30.7 ± 6.1 kg/m2 vs. 55.6 ± 20.0 kg/m2. For total concentrations, Cmax and Cmin were 195.5 ± 78.4 μg/ml and 26.6 ± 25.0 μg/ml for Group 1 and 244.2 ± 91.3 μg/ml and 42.2 ± 34.7 μg/ml for Group 2, respectively. Vss was 24% larger and CL was 7% faster in Group 2. For unbound concentrations, Cmax and Cmin were 86.4 ± 48.9 μg/ml and 8.6 ± 8.3 μg/ml for Group 1 and 96.2 ± 41.8 μg/ml and 9.5 ± 7.4 μg/ml for Group 2, respectively. Vss was 34% larger and CL was 27% faster in Group 2. None of these PK differences were statistically significant between groups. However, protein binding was significantly higher in Group 2 (71.7% vs. 64.0%, p<0.001). PTA was > 90% for 2 grams q8h in Group 1 and 3 grams q8h in Group 2 at MICs ≤ 8 μg/ml for 40% fT>MIC and at MICs ≤ 4 μg/ml for 60% fT>MIC.
Cefazolin pharmacokinetic parameters were not significantly different between patient groups, but protein binding was significantly higher in patients > 120 kg. Cefazolin 3 grams q8h in patients > 120 kg provides similar PD exposures to 2 grams q8h in patients < 120 kg.
S. C. Cheatham,
S. Utley, None
M. Campion, None
T. F. Murrey, None
D. P. Healy, None
M. F. Wack, None
A. Browning, None
J. Jeffery, None
E. K. Chung, None
M. Kays, None
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