Table 1. Summary of Previously Published Morphine IV Models.

Publication	Demographics	PK Model	Parameterization
Bouwmeester4	Number of subjects: 184 Number of samples: 1856 Mean age: 195 (range: 0-1070) days Mean body weight: 5.9 (range: 1.9-16.8) kg	1-Compartment Model	$\mathbf{\text{tvCL}}=\mathbf{\text{CLstd}}•{\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)}^{\mathbf{0.75}}•\frac{{\mathbf{\text{PMA}}}^{\mathbf{\text{HillCL}}}}{{\mathbf{\text{PMA}}}^{\mathbf{\text{HillCL}}}+{{\mathbf{\text{CLmat}}}_{\mathbf{50}}}^{\mathbf{\text{HillCL}}}}\mathbf{\text{Liter}}/\mathbf{\text{hour}}$ $\mathbf{\text{tvV}}\mathbf{1}=\mathbf{V}\mathbf{1}\mathbf{\text{std}}•\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)•(\mathbf{1}+\mathbf{\beta }\mathbf{\text{vol}}•{\mathrm{e}}^{-\mathbf{\text{PNA}}•\frac{\mathbf{\text{Ln}}\left(\mathbf{2}\right)}{\mathbf{\text{Tvol}}}})\mathbf{\text{Liter}}$
Holford5	Number of subjects: 875 Number of samples: 1598 PNA: 0.27 (SD: 0.26, range: 0–2.84) weeks, PMA: 27.35 (SD: 2.31, range: 23–32) weeks Body weight: 1.04 (SD: 0.35, range: 0.42–2.44) kg with data from Bouwmeester4	2-Compartment Model	$\mathbf{\text{tvCL}}=\mathbf{\text{CLstd}}•{\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)}^{\mathbf{0.75}}•\frac{{\mathbf{\text{PMA}}}^{\mathbf{\text{HillCL}}}}{{\mathbf{\text{PMA}}}^{\mathbf{\text{HillCL}}}+{{\mathbf{\text{CLmat}}}_{\mathbf{50}}}^{\mathbf{\text{HillCL}}}}\mathbf{\text{Liter}}/\mathbf{\text{hour}}$ $\mathbf{\text{tvV}}\mathbf{1}=\mathbf{V}\mathbf{1}\mathbf{\text{std}}•\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)•(\mathbf{1}+\mathbf{\beta }\mathbf{\text{vol}}•{\mathbf{e}}^{-\mathbf{\text{PNA}}•\frac{\mathbf{\text{Ln}}\left(\mathbf{2}\right)}{\mathbf{\text{Tvol}}}})\mathbf{\text{Liter}}$ $\mathbf{\text{tvQ}}\mathbf{2}=\mathbf{Q}\mathbf{2}\mathbf{\text{std}}•{\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)}^{\mathbf{0.75}}\mathbf{\text{Liter}}/\mathbf{\text{hour}}$ $\mathbf{\text{tvV}}\mathbf{2}=\mathbf{V}\mathbf{2}\mathbf{\text{std}}•\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)•(\mathbf{1}+\mathbf{\beta }\mathbf{\text{vol}}•{\mathbf{e}}^{-\mathbf{\text{PNA}}•\frac{\mathbf{\text{Ln}}\left(\mathbf{2}\right)}{\mathbf{\text{Tvol}}}})\mathbf{\text{Liter}}$
Knibbe7	Number of subjects: 248 Number of samples: 792 Median body weight: 3.58kg (25–75 percentile: 2.2 - 7.0); Median PNA: 33 (25–75 percentile: 0.95 - 203) days Median PMA: 41.9 (25–75 percentile: 35.6 - 62.6) weeks	2-Compartment Model	tvCL = CLstd•(Wt)1.44 Liter/hour tvV1 = V1std•(Wt)Liter tvQ2 = Q2std Liter/hour tvV2 = V2std•(Wt)Liter
Wang8	Number of subjects: 475 Number of samples: 9494 Body weight range: 0.56-85 kg Age range: 0.1 days-36 years	2-Compartment Model	$\mathbf{\text{tvCL}}=\mathbf{\text{CLstd}}•{\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)}^{\mathbf{k}}\mathbf{\text{Liter}}/\mathbf{\text{hour}}$ $\mathbf{k}={\mathbf{k}}_{\mathbf{0}}-\frac{{\mathbf{k}}_{\mathbf{\text{max}}}•{\mathbf{\text{Wt}}}^{\mathbf{4.62}}}{{\mathbf{k}}_{\mathbf{50}}^{\mathbf{4.62}}+{\mathbf{\text{Wt}}}^{\mathbf{4.62}}}$ $\mathbf{\text{tvV}}\mathbf{1}=\mathbf{V}\mathbf{1}\mathbf{\text{std}}•\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)\mathbf{\text{Liter}}$ $\mathbf{\text{tvQ}}\mathbf{2}=\mathbf{Q}\mathbf{2}\mathbf{\text{std}}•\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)\mathbf{\text{Liter}}/\mathbf{\text{hour}}$ $\mathbf{\text{tvV}}\mathbf{2}=\mathbf{V}\mathbf{2}\mathbf{\text{std}}•\left(\frac{\mathbf{\text{Wt}}}{\mathbf{70}}\right)\mathbf{\text{Liter}}$
Lotsch	Number of subjects: 8 Number of samples: 152 Mean PNA: 26.4 years Mean body weight: 70.5 kg	3-Compartment Model	(No body weight, PMA and PNA was used for parameterization)

PMA: post menstrual age

PNA: post-natal age