TABLE 3.
Population pharmacokinetic estimates of amoxicillin-clavulanic acid
| Parametera | Estimate | Median bootstrap estimate | 2.5th percentile from bootstrap estimateb (n = 1,000) | 95th percentile from bootstrap estimateb (n = 1,000) |
|---|---|---|---|---|
| Amoxicillin | ||||
| CL (liters/h/70 kg) | 17.97 | 17.83 | 15.33 | 21.30 |
| V1 (liters/70 kg) | 9.07 | 9.00 | 6.41 | 11.66 |
| V2 (liters/70 kg) | 5.43 | 5.75 | 3.57 | 13.45 |
| V3 (liters/70 kg) | 11.24 | 11.00 | 7.01 | 13.78 |
| Q1 (liters/h/70 kg) | 35.88 | 34.73 | 12.03 | 60.09 |
| Q2 (liters/h/70 kg) | 5.52 | 5.36 | 1.49 | 8.03 |
| θ in (CYSC/MCYSC)Θ | −0.54 | −0.54 | −1.01 | −0.14 |
| θ in COVVASO = (1 + θ) | −0.18 | −0.18 | −0.28 | −0.07 |
| BSV on CL (% CV) | 18.9 | 18.1 | 8.10 | 28.6 |
| BSV on V1 (% CV) | 48.6 | 46.8 | 30.9 | 66.7 |
| BOV on CL (% CV) | 14.6 | 13.8 | 7.70 | 20.2 |
| Residual error (% CV) | 28.7 | 28.4 | 23.4 | 33.1 |
| Clavulanic acid | ||||
| CLclav (liters/h/70 kg) | 12.20 | 12.09 | 10.54 | 14.55 |
| V1clav (liters/70 kg) | 11.60 | 11.39 | 8.42 | 13.76 |
| V2clav (liters/70 kg) | 9.85 | 10.22 | 8.05 | 13.87 |
| Q1clav (liters/h/70 kg) | 6.22 | 6.81 | 3.94 | 23.9 |
| θ in CYSCOV = (CYSC/MCYSC)Θ | −0.37 | −0.36 | −0.85 | −0.08 |
| BSV on CLclav (% CV) | 15.6 | 15.6 | 7.8 | 22.6 |
| θ in BSV on V1clav = θ*BSV on V1 | 0.77 | 0.77 | 0.40 | 0.97 |
| θ in BOV on CLclav = θ*BOV on CL | 0.52 | 0.48 | −0.02 | 1.34 |
| Residual error (% CV) | 35 | 34 | 27 | 40 |
| Amoxicillin-clavulanic acid | ||||
| Hill coefficientc | 1 | 1 | 1 | 1 |
| TM50 (wk) | 39.90 | 39.10 | 20.66 | 64.29 |
a
Abbreviations: CL, clearance; clav, clavulanic acid; V1, central volume of distribution; V2 and V3, peripheral volumes of distribution; Q1 and Q2, intercompartmental clearances; θ, model parameter in NONMEM code; CYSCOV, cystatin C covariate on clearance; CYSC, plasma cystatin C value; MCYSC, median plasma cystatin C value; COVVASO, vasopressor covariate on clearance (θ = 0 if no coadministration with vasopressors); BSV, between-subject variability; BOV, between-occasion variability; CV, coefficient of variation; TM50, maturation half-life.
b
Nonparametric bootstrap of 953 successful runs.
c
Fixed value.