Table S1: Estimated Allometric Coefficients and Exponents for Six Drugs (Model 1)

Table S1: Estimated allometric coefficients and exponents for six drugs (model 1)

Drugs / Coefficient (mL/min) / Exponent / Correlation (r2)
Morphine / 2.7 (2%) / 1.673 (3%) / 0.914
Propofol / 34.1(0.3%) / 0.983 (8%) / 0.751
Vancomycin / 1.0 (7%) / 1.108 (5%) / 0.902
Amikacin / 1.0 (8%) / 1.195 (5%) / 0.920
Alfentanil / 6.4 (2%) / 1.057 (7%) / 0.809
Oxycodone / 23.2 (0.5%) / 0.826 (11%) / 0.730

Numbers in parenthesis are coefficient of variation (%CV)

Table S2: Estimated maturation model parameters for six drugs (model 3)

Drugs / CLstd (mL/min) / PMA50 (weeks) / HillCL
Morphine / 1857 (8%) / 66 (5%) / 3.84 (7%)
Propofol / 1894 (7%) / 32 (4%) / 9.46 (28%)
Vancomycin / 104 (8%) / 45.4 (8%) / 3.45 (17%)
Amikacin / 123 (5%) / 40.7 (5%) / 4.71 (10%)
Alfentanil / 426 (6%) / 52 (17%) / 4.78 (14%)
Oxycodone / 766 (7%) / 37.6 (2%) / 24.33 (41%)

Numbers in parenthesis refer to the estimated parameter precision expressed as coefficient of variation (%CV) and are calculated as %CV = 100 x SE/(estimated parameter value) where SE represents the asymptotic standard error of the parameter estimate.

Table S3: Estimated body weight dependent (BDE) model parameters for six drugs

(model 4)

Drugs / Coefficient (mL/min) / Exponent L / Exponent M
Morphine / 1945 (11%) / 1.564 (2%) / -0.146 (14%)
Propofol / 1405 (9%) / 1.018 (6%) / -0.375 (16%)
Vancomycin / 89 (10%) / 1.117 (3%) / -0.179 (15%)
Amikacin / 96 (6%) / 1.133 (2%) / -0.245 (10%)
Alfentanil / 381 (8%) / 1.547 (5%) / -0.353 (12%)
Oxycodone / 579 (14%) / 0.767 (14%) / -0.232 (35%)

Numbers in parenthesis refer to the estimated parameter precision expressed as coefficient of variation (%CV) and are calculated as %CV = 100 x SE/(estimated parameter value) where SE represents the asymptotic standard error of the parameter estimate.

Table S4: Estimated intercepts and slopes for segmented model (model 5)

Drugs / Segment 1 / Segment 2 / Segment 3
Intercept / Slope / Intercept / Slope / Intercept / Slope
Morphine / 2.74 / 1.168 (16%) / 0.02 / 5.381 (27%) / 19.2 / 1.127 (9%)
Propofol / 6.37 / 2.307 (11%) / 170.2 / 0.527 (17%) / NA / NA
Vancomycin / 0.68 / 1.204 (15%) / 0.07 / 3.211 (24%) / 16.1 / 0.363 (31%)
Amikacin / 0.58 / 1.939 (4%) / 20.9 / 0.338 (21%) / NA / NA
Alfentanil / 0.66 / 2.490 (8%) / 17.3 / 0.729 (10%) / NA / NA
Oxycodone / 1.24 / 3.165 (29%) / 23.8 / 0.832 (11%) / NA / NA

Numbers in parenthesis are coefficient of variation (%CV)

Figure S1: An allometric plot (body weight vs clearance) of morphine developed from preterm neonates to adult clearance.

Figure S2: Observed and predicted clearance of morphine (CLnorm), standardized to (BWi/70 kg)0.75 plotted against post-menstrual age (PMA) in weeks (wk). The solid line represents a fit to the nonlinear maturation model.

Figure S3: Observed and predicted clearance clearances (CL) of morphine plotted against body-weight (kg). The solid line represents a fit to the body-weight dependent allometric exponent model.

Figure S4: The observed and predicted clearance of morphine from single and multiple slopes.

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