TABLE 1

Parameter estimates for the final model

Parameter ValueRSE
%
Structural parameters
 ka (pmol/min)0.7606
 kPG,f (min−1)0.0032710
Embedded Image
 kPS,f,0 (min−1)0.42257
 t50 (min)1.4270
 kP,e (min−1)0.018510
 kG,e (min−1)0.0074317
 kS,e (min−1)0.00066466
 VP (nl)21824
 VG (nl)12525
 VS (nl)26220
 fP,e (%)0.11326
 fG,e (%)0.090024
 fS,e (%)3.7471
Stochastic parameters homogenate
 Variance of paracetamol proportional residual error (−)0.19117
 Variance of paracetamol-glucuronide proportional residual error (−)0.27917
 Variance of paracetamol-sulfate proportional residual error (−)0.052129
 Correlation of paracetamol and paracetamol-glucuronide proportional residual error (−)−0.22013a
 Correlation of paracetamol-glucuronide and paracetamol-sulfate proportional residual error (−)−0.035815a
 Variance of paracetamol additive residual error (pmol/larva)0.0046193
 Variance of paracetamol-glucuronide additive residual error (pmol/larva)0.013171
Stochastic parameters blood
 Variance of paracetamol additive residual error (pmol/nl)0.014870
 Variance of paracetamol-glucuronide proportional residual error (−)0.39350
 Variance of paracetamol-sulfate proportional residual error (−)0.99433
Stochastic parameters excreted compound
 Variance of paracetamol additive residual error (pmol/larva)0.00020741
 Variance of paracetamol-glucuronide proportional residual error (−)0.67823
 Variance of paracetamol-sulfate proportional residual error (−)0.94147
 Variance of paracetamol-sulfate additive residual error (pmol/larva)0.00113110
  • fG,e, recovery fraction excreted paracetamol-glucuronide; fP,e, recovery fraction excreted paracetamol; fS,e, recovery fraction excreted paracetamol-sulfate; ka, absorption rate constant; kG,e, paracetamol-glucuronide excretion rate; kP,e, paracetamol excretion rate; kPG,f, metabolic formation rate for glucuronidation; kPS,f,0, metabolic formation rate for sulfation at time point 0; kS,e, paracetamol-sulfate excretion rate; VG, paracetamol-glucuronide distribution volume; VP, paracetamol distribution volume; VS, paracetamol-sulfate distribution volume; t50, time at which time-dependent metabolic formation rate for sulfation is at 50%.

  • a RSE of the estimate for covariance.