TABLE 1

Population PK parameters estimated for healthy subjects and subjects with renal impairment

ParameterHS modelMDRD-eGFR modelaCG-CLCR modelb
Mean% RSEMean% RSEMean% RSE
Typical CL (liters/h)5.591.95.662.04.832.9
First slope of renal function marker on CL (MDRD-eGFR or CG-CLCR of <100)0.008571.40.008801.6
Second slope of renal function marker on CL (MDRD-eGFR or CG-CLCR of ≥100)0Fixed0.0040417.9
Typical V1 (liters)7.742.57.582.77.582.7
Exponent of body wt on V10.57111.30.57516.5
Q2 (liters/h)5.443.65.454.35.454.5
Typical V2 (liters)5.362.95.542.55.542.5
Exponent of body wt on V20.72713.10.73012.9
Q3 (liters/h)0.076215.20.097115.90.096917.0
V3 (liters)0.5948.70.6827.70.6818.3
Fraction of urinary recovery0.6591.2c
IIV for CL (% CV)12.037.217.318.311.918.7
IIV for V1 (% CV)16.327.119.519.419.319.7
IIV for V2 (% CV)9.734.114.142.714.242.6
Proportional residual error in plasma (% CV)13.614.012.014.112.014.1
Proportional residual error in urine (% CV)17.919.3
  • a If MDRD-eGFR < 100 ml/min/1.73 m2, then CL = 5.66 × [1 + 0.00857 × (eGFR − 100)]; if MDRD-eGFR ≥ 100 ml/min/1.73 m2, then CL = 5.66; V1 = 7.58 × (body weight/70)0.571; V2 = 5.54 × (body weight/70)0.727.

  • b If CG-CLCR < 100 ml/min, then CL = 4.83 × [1 + 0.00880 × (CLCR − 100)]; if CG-CLCR ≥ 100 ml/min, then CL = 4.83 × [1 + 0.00404 × (CLCR − 100)]; V1 = 7.58 × (body weight/70)0.575; V2 = 5.54 × (body weight/70)0.730.

  • c —, urine concentration data for cefiderocol were not used for the modeling.