Table 3.
Population parameter estimates (from NONMEM V and S-ADAPT) of the three compartment model with first-order nonrenal elimination and parallel first-order and mixed-order renal elimination for piperacillin
| Parameter | NONMEM (PPV = BSV + BOV) | S-ADAPT (PPV) |
|---|---|---|
| CLNR (for 70 kg)* (l h−1) | 4.40 | 4.61 (21.4%) |
| CLR (for 70 kg)* (l h−1) | 5.70 (9.62%‡,¶) | 6.64 (11.1%) |
| Vmax (for 70 kg)* (mg h−1) | 170 (50.4%§) | 67.9 (17.2%) |
| Km (mg l−1) | 49.7 (150%§) | 11.1 (134%) |
| Vss (for 70 kg)† (l) | 12.7 (13.5%‡) | 13.3 |
| V1 (for 70 kg)† (l) | 7.00 | 7.15 (13.9%) |
| V2 (for 70 kg)† (l) | 2.95 | 3.28 (2.2%) |
| V3 (for 70 kg)† (l) | 2.71 | 2.92 (14.9%) |
| CLicshallow (for 70 kg)* (l h−1) | 12.7 | 16.7 (3.5%) |
| CLicdeep (for 70 kg)* (l h−1) | 1.28 | 1.65 (22.5%) |
| CVC | 12.5% | 12.8% |
| SDC (mg l−1) | 0.447 | 0.415 |
| CVAU | 24.6% | 17.7% |
| SDAU (m)g | 3.89 | 4.18 |
PPV (population parameter variability), CVC is the proportional and SDC is the additive residual error component for the plasma concentrations. CVAU is the proportional and SDAU is the additive residual error component for the amounts excreted in urine (see methods section for details).
The allometric model with a standard body weight of 70 kg and an exponent of 0.75 was used to scale the clearance terms and Vmax.
The allometric model with a standard body weight of 70 kg and an exponent of 1.0 was used to scale the volume of the central and both peripheral compartments.
Correlation between pairs of random effects: r(CLtot,Vss) = 0.84.
r(Vmax,Km) = 0.99.
PPV for CLNR and CLR combined (see methods for details). CLNR, nonrenal clearance describing the first-order nonrenal elimination; CLR, renal clearance describing the first-order renal elimination; Vmax, maximum rate of elimination for the mixed-order renal elimination; Km, plasma concentration that results in a rate of 50% of Vmax; Vss, Volume of distribution at steady-state; V1, volume of central compartment; V2, volume of shallow peripheral compartment; V3, volume of deep peripheral compartment; CLicshallow, intercompartmental clearance between the central and shallow peripheral compartment; CLicdeep, intercompartmental clearance between the central and deep peripheral compartment.