Table 3.
Median individual Bayesian posterior parameter estimates for the 11 tigecycline and 1 meropenem patient plus covariate-based parameter estimates for 1 tigecycline and 3 meropenem patients used to estimate pharmacodynamic exposure
| Antibiotic/patient number | Pharmacokinetic parameter estimatesa | |||
|---|---|---|---|---|
| CL (L/h) | Vc (L) | kcp (h−1) | kpc (h−1) | |
| Tigecycline | ||||
| 3 | 22.3 | 118.9 | 5.688 | 1.883 |
| 4 | 37.0 | 100.2 | 1.046 | 0.375 |
| 5 | 19.0 | 89.1 | 1.945 | 1.269 |
| 6 | 15.0 | 79.3 | 2.575 | 0.299 |
| 7 | 37.0 | 100.3 | 1.045 | 0.376 |
| 8 | 37.0 | 100.3 | 1.045 | 0.375 |
| 9 | 22.5 | 149.0 | 3.583 | 1.986 |
| 10 | 19.5 | 89.1 | 4.152 | 1.268 |
| 11 | 24.2 | 26.1 | 7.885 | 0.110 |
| 12 | 19.4 | 21.9 | 4.195 | 0.490 |
| 16 | 19.2 | 88.6 | 3.540 | 1.262 |
| 17b | 17.1 | N/A | N/A | N/A |
| Meropenem | ||||
| 1c | 10.2 | 16.7 | 0.487 | 0.647 |
| 2c | 9.5 | 16.5 | 0.487 | 0.647 |
| 4 | 22.0 | 40.9 | 9.95 | 4.41 |
| 15c | 6.3 | 14.3 | 0.487 | 0.647 |
CL clearance, Vc volume of distribution of the central compartment, kcp and kpc intercompartment transfer constants between central and peripheral compartments and vice versa, respectively, fAUC/MIC free area under the curve to minimum inhibitory concentration ratio, fT > MIC free time above the minimum inhibitory concentration, N/A not available
aAll pharmacokinetic parameter estimates are derived from the Bayesian posterior model fits in Pmetrics, except for patients 1, 2, 15, and 17 (see footnotes)
bConcentration data not available for this patient. Exposure estimated using a covariate-based model [15], as 24-h maintenance dose divided by CL, where CL = [(9.6 + (10.2 × BSA − 1.73))] + [(0.0638 × (CrCL − 100)], where BSA is body surface area and CrCL is baseline creatinine clearance
cConcentration data not available for two patients (1 and 2), and observed versus predicted concentrations were poorly fit for patient 15. Exposure estimated using a covariate-based model [13], based on clearance [CL = (0.392 + 0.003 × CrCL)], volume of the central compartment [Vc = 0.239 × adjusted body weight, where adjusted body weight = IBW + [0.4 × (ABW − IBW) or if adjusted body weight is < 20% above ideal body weight (IBW), then actual body weight used (ABW)], and median population estimates for kcp and kpc