Article Figures & Data
Figures
- Fig. 1.
Final population PK model. Vc, volume of the central compartment; Vp, volume of the peripheral compartment; A, slope of the relationship between VAN central clearance and creatinine clearance (CCL); B, intercept of the relationship between VAN central clearance and creatinine clearance; Cld, distributional clearance.
- Fig. 2.
Weighted residuals versus observed serum concentrations of VAN.
- Fig. 3.
Fitted (line) and observed (solid circle) VAN serum concentrations in a representative patient.
- Fig. 4.
Relationship between observed and model-predicted VAN serum concentrations using demographic data only.
- Fig. 5.
Relationship between observed and model-predicted VAN serum concentrations using demographic data and the results of a previous peak and trough.
Tables
- Table 1.
Demographic data and laboratory values
Characteristic Primary population Naive population No. of patients (no. of serum concns) 78 (256) 19 (84) No. male/no. female 40/38 11/8 Median age in yr (range) 7 (0.01–18) 8.5 (0.3–18) Median wt in kg (range) 25 (0.93–74) 32 (5.5–84.9) Serum creatinine level ± SD (μmol/ml) 47.8 ± 24.4 37.8 ± 15.7 Creatinine clearance ± SD (ml/min adjusted for 1.73 m2)a 138.6 ± 49.3 160.7 ± 28.4 ↵a Calculated using Schwartz's formula (13).
- Table 2.
Average population PK parameters of VAN and their associated interindividual variabilitya
Type of value Vc Vp A B Cld Liters/30 kg Liters/kg Liters/30 kg Liters/kg ml/min/30 kg ml/min/kg Liters/h/30 kg Liters/h/kg Mean 8.3 0.27 4.8 0.16 0.46 9 0.3 4.9 0.16 Range 0.9–18.5 0.03–0.62 0.3–10.1 0.01–0.37 0.06–1.08 0.3–10.1 0.01–0.34 CV (%) 42 43 45 ND 43 ↵a Residual variability in VAN serum concentrations (includes the intraindividual variability and all experimental errors) was 6.5%. Values shown per kilogram rather than per 30 kg are adjusted per kilogram of body weight. Vc, volume of the central compartment; Vp, volume of the peripheral compartment;A (no unit), slope of the relationship between VAN central clearance and creatinine clearance; B, intercept of the relationship between VAN central clearance and creatinine clearance; Cld, VAN distributional clearance; CV, coefficient of variation; ND, not determined.
- Table 3.
Average calculated population PK parameters of VAN and their associated interindividual variabilitya
Type of value Vss CL t1/2 Mean 0.43 liter/kg 0.103 liter/h/kg 3.9 h CV 43% 45% 57% ↵a Vss, total volume of distribution; CL, total plasma clearance; t1/2, terminal elimination half-life; CV, coefficient of variation.
- Table 4.
Precision and bias (±95% confidence interval) of the population PK model compared with those obtained using the nomogram previously used in our institutiona
Method Bias (mg/liter) Precision (mg/liter) Peak Trough Peak Trough Previously used nomogram −11.4 (±2.38) −3.56 (±0.99) 11.15 (±2.38) 4.07 (±0.82) Population PK model (no prior VAN serum concns were used) −0.058 (±2.15) −0.63 (±1.11) 4.1 (±1.41) 2.19 (±0.72) Population PK model (VAN serum concns were used as prior information) −0.66 (±2.67) 0.45 (±1.29) 4.41 (±1.82) 2.01 (±0.94) ↵a The absence of bias in the model was demonstrated using the Wilcoxon signed rank test.
