Tamara van Donge

Simplification of methadone dosing in preterm neonates 95 5 Table S1: Parameters for final population PK model for (R)- and (S)-methadone. RSE; Relative standard error, CI; Confidence interval, Ka; Absorption rate constant, V d ; Volume of distribution, CL; Clearance, F; bioavailability (unknown because only oral administration), *CV; coefficient of variation (%) presented instead of RSE for values for inter-individual variability. Parameter (R)-methadone (S)-methadone Estimate % RSE Bootstrap analysis Estimate % RSE Bootstrap analysis Median 95% CI Median 95% CI Population parameters K a (h -1 ) 1.73 0.57 1.69 1.15-2.90 2.65 0.08 1.20 0.79-1.89 V d /F (L) 26.9 1.89 27.5 21.9-33.2 18 0.13 16.73 13.77-19.95 CL/F (L/h) 0.24 0.04 0.25 0.18-0.33 0.17 5.24 0.18 0.12-0.23 GA effect 5.29 1.75 5.86 3.14-9.07 5.16 0.46 4.99 1.94-8.74 Inter-individual variability - % CV* K a (h -1 ) 0.05 - - - 0.05 - - - V d /F (L) 0.39 69 0.36 0.21-0.56 0.30 59 0.33 0.16-0.54 CL/F (L/h) 0.20 47 0.19 0.009-0.4 0.19 46 0.18 0.02-0.42 Residual variability Proportional error 0.106 - 0.101 0.07-0.13 0.115 - 0.102 0.06-0.13