TABLE 2.
Population pharmacokinetic parameters of meropenem from the base and final model
| Base model (OFV = 1,382.7) |
Final modelb (OFV = 1,334.9) |
|||
|---|---|---|---|---|
| Parametera | Estimate (% RSEa) | Estimate (% RSEa) |
% Shra | Median (95% CIa) of bootstrap estimate |
| Fixed-effect parameters | ||||
| CL (L/h) | 4.8 (11.9) | 5.16 (9.8) | 5.19 (4.22 to 6.21) | |
| θ1 | 0.016 (8.9) | 0.016 (0.012 to 0.018) | ||
| VC (L) | 11.4 (11.5) | 11.1 (10.8) | 11.1 (7.89 to 12.79) | |
| θ2 | −0.255 (30.5) | −0.258 (−0.418 to −0.103) | ||
| VP (L) | 14.6 (12.0) | 10.3 (31.7) | 10.49 (7.35 to 14.72) | |
| θ3 | 11.3 (43.1) | 11.42 (3.54 to 22.57) | ||
| Q (L/h) | 10.5 (30.4) | 9.37 (38.4) | 9.40 (6.06 to 22.57) | |
| Interindividual variability (IIV, % CVa) | ||||
| IIV on CL | 86.1 (9.5) | 60.5 (11.4) | 1.0 | 59.4 (45.7 to 72.8) |
| IIV on VC | 30.0 (38.9) | Fixed to 0 | ||
| IIV on VP | 63.7 (18.8) | 47.7 (22.1) | 36.3 | 45.7 (23.7 to 66.5) |
| IIV on Q | Fixed to 0 | |||
| Residual variability (%) | ||||
| Proportional | 24.1 (11.0) | 26.0 (8.3) | 13 | 25.6 (21.1 to 29.7) |
a
% RSE, percentage of relative standard error; % Shr, percentage of shrinkage; % CV, percentage of coefficient of variation; OFV, minimum objective function value; CI, confidence interval; CL, total clearance; VC, central volume of distribution; VP, the peripheral volume of distribution; Q, intercompartment clearance; CLCR-CG, creatinine clearance estimated by Cockcroft-Gault equation; ALB, serum albumin (g/dL); Shock, a clinical state requiring vasopressors or inotropes to maintain a mean arterial pressure greater than 65 mm Hg.
b
The final PK model parameters: