TABLE 2.
Final population PK model for ceftarolinea
| Parameterb | Estimate | % SEM | Bootstrap mean (90% confidence interval) |
|---|---|---|---|
| CLi (liters/h)c | 11.6 | 9.24 | 11.5 (9.61, 13.1) |
| CLi-CLCR power | 0.441 | 10.8 | 0.443 (0.361, 0.518) |
| CLi-age slope | −0.0883 | 17.0 | −0.0902 (−0.111, −0.0698) |
| CLi shift for POPj | 4.11 | 17.7 | 4.16 (3.11, 5.28) |
| Km (mg/liter) | 9.62 | 26.6 | 9.58 (6.79, 13.6) |
| CLlin (liters/h)d | 3.06 | 17.7 | 3.16 (2.09, 4.20) |
| CLlin-CLCR power | 0.343 | 17.5 | 0.333 (0.206, 0.424) |
| Vc (liters)e | 8.67 | 4.93 | 8.64 (8.11, 9.25) |
| Vc shift for POPj | 7.02 | 22.1 | 6.97 (5.01, 8.69) |
| CLd (liters/h)f | 8.59 | 6.07 | 8.59 (7.39, 10.0) |
| CLd shift for males | 4.88 | 17.1 | 5.04 (3.42, 6.90) |
| Vp (liters)g | 11.7 | 5.02 | 11.6 (10.5, 12.7) |
| Vp shift for males | 2.87 | 16.7 | 2.97 (2.05, 3.90) |
| ω2CLi | 30.2% CVh | 21.5 | 29.6% CV (23.9, 35.5) |
| Covariance (CLi, Km) | −0.0927 (r2 = 0.196) | 55.6 | −0.0780 (−0.160, 0.0001) |
| ω2Km | 67.0% CV | 28.6 | 65.0% CV (50.5, 77.4) |
| ω2Vc | 43.5 | 25.2 | 43.4% CV (34.7, 52.2) |
| ω2CLd | 31.8% CV | 25.8 | 31.8% CV (24.8, 39.1) |
| Covariance (CLd, Vp) | 0.0643 (r2 = 0.959) | 25.5 | 0.0645 (0.0412, 0.0929) |
| ω2Vp | 20.6% CV | 26.7 | 21.2% CV (17.2, 25.4) |
| σ2Additive | 0.0392 | 8.74 | 0.0387 (0.0331, 0.0440) |
| σ2CCV | 0.00180 | 53.1 | 0.0019 (0.0011, 0.0031) |
Data were obtained from reference 8.
CCV, constant coefficient of variation; CLd, distribution clearance for the peripheral compartment for ceftaroline; CLi, intrinsic ceftaroline clearance for the saturable elimination pathway; CLlin, linear ceftaroline clearance; Km, ceftaroline concentration producing 50% of CLi; ω2, interindividual variability; σ2, residual variability; Vc, ceftaroline central volume of distribution; Vp, = volume of distribution for the peripheral compartment for ceftaroline.
Population mean CLi (liters/h) = 11.6 · (CLCRj/102)0.441 −0.0883 · (agej − 36) + 4.11 · POPj, where POPj is an indicator variable in the jth subject with a value of 1 for phase 2/3 patients and 0 otherwise.
Population mean CLlin (liters/h) = 3.06 · (CLCRj/102)0.343.
Population mean Vc (liters) = 8.67 + 7.02 · POPj.
Population mean CLd (liters/h) = 8.59 + 4.88 · MALEj, where MALEj is an indicator variable in the jth subject with a value of 1 for males and 0 for females.
Population mean Vp (liters) = 11.7 + 2.87 · MALEj.
CV, coefficient of variation.