Table 2.
Parameter estimates (pharmacokinetic parameters for meropenem and microdialysis methodology-related parameters) including bootstrap results of the final model of meropenem in obese and non-obese patients
| Parameter | Final model | Bootstrapa |
|---|---|---|
| Estimate (RSEb, %) | Median (95% CI) | |
| Structural and covariate parameters | ||
| CLRfilt scaled via CLCRCG_ABWc, L/h | 5.48 (29.0) | 5.34 (1.01–8.91) |
| CLnonfilt scaled via ABWd, L/h | 4.99 (32.5) | 5.13 (1.91–9.91) |
| MAP_CLnonfilte,% | 0.618 (37.1) | 0.594 (0.141–2.01) |
| V1 scaled via ABWd [L] | 7.24 (10.7) | 7.24 (5.67–8.68) |
| Q1d scaled via ABWd [L/h] | 31.3 (10.2) | 31.4 (26.1–38.5) |
| V2d scaled via ABWd [L] | 9.39 (8.00) | 9.37 (7.96–11.1) |
| Q2d scaled via ABWd [L/h] | 3.06 (34.3) | 3.20 (0.73–5.56) |
| V3d scaled via ABWd [L] | 2.14 (19.2) | 2.14 (1.32–3.06) |
| TF, % | 37.2 (11.4) | 37.1 (29.7–47.4) |
| ANAE_TFf, % | 19.0 (20.4) | 19.1 (11.8–26.4) |
| RROBE, % | 31.0 (10.1) | 31.0 (25.8–37.6) |
| RRNOBE, % | 55.3 (9.90) | 55.7 (45.6–65.8) |
| Interindividual variability parameters, %CV | ||
| CL | 20.8 (13.4) | 19.9 (13.9–25.4) |
| V1 | 34.1 (18.9) | 32.9 (19.2–48.4) |
| Q1 | 43.1 (19.3) | 41.8 (22.0–57.7) |
| V2 | 32.2 (15.6) | 31.5 (19.3–40.5) |
| TF | 46.2 (15.0) | 44.9 (31.4–58.6) |
| Coefficients of correlation | ||
| V2–Q1 | 0.630 (41.1) | 0.624 (0.140–0.859) |
| Q1–TF | 0.281 (27.1) | 0.298 (0.0343–0.586) |
| TF–RR | − 0.764 (31.2) | − 0.797 (− 0.938 to − 0.477) |
| Microdialysis technique-related variability parameters | ||
| σ2Interindividual RR | 0.388 (38.1) | 0.355 (0.341–0.820) |
| σ2Intercatheter RR | 0.157 (49.8) | 0.151 (0.214–0.583) |
| σ2Intracatheter RR | 0.515 (44.9) | 0.519 (0.373–1.01) |
| Residual variability parameters | ||
| σadditive, plasma, mg/L | 0.0600 (28.2) | 0.0603 (0.0187–0.140) |
| σproportional, plasma, %CV | 8.43 (12.3) | 8.25 (6.24–10.4) |
| σproportional, microdialysis, %CV | 18.3 (9.70) | 17.9 (14.9–21.6) |
| σproportional, retrodialysis, %CV | 2.3 FIXg | 2.3 FIXg |
ABW adjusted body weight, ANAE_TF anesthesia effect on TF, CI confidence interval, CL clearance, CLCRCG_ABW creatinine clearance calculated via Cockcroft-Gault based on ABW, CLnonfilt clearance accounting for the remaining elimination scaling with ABW, CLRfilt renally filtered part of CL related to CLCRCG_ABW, CMT1/CMT2/CMT3 central/peripheral/deep peripheral compartment, CV coefficient of variation, MAP mean arterial pressure, OBE obesity, Q1/Q2 intercompartmental flow of meropenem from CMT1/CMT2 to CMT2/CMT3, RROBE/RRNOBE relative recovery for obese/non-obese patients, RSE relative standard error, TF tissue factor, V1/V2/V3 volume of distribution parameters for CMT1/CMT2/CMT3 of meropenem, σ residual unexplained variability, σ2 variance associated with retrodialysis
aConvergence rate of nonparametric bootstrap (n = 1000): 91.6%
bRSE of random effects are reported on approximate standard deviation scale
cScaled (linear relationship) with the ratio of individual CLCRCG_ABW to the median CLCRCG_ABW in overall population (87.9 mL/min)
dAllometrically scaled with ABW centered to median in overall population (70.5 kg) with exponent of 1 for volumes and 0.75 for flows
eChange of CLnonfilt per mmHg deviation of MAP from 75 mmHg (linear relationship)
fChange of TF after anesthesia
gFixed to interassay variability