Table 3.

Assumptions and values used for the randomisation of factors used in the study, based on data from in vitro experiments

Factor	Assumption	References
CYP3A4	Log-normal distribution with a geometric SD of 1.5 (average value of the SDs reported in the literature)	[68, 71, 72]
CYP2J2	Log-normal distribution with a geometric SD of 2.5 (based on the CYP2J2 mRNA distribution in postnatal liver samples)	[69]
CYP-independent hydrolysis	Log-normal distribution and a geometric SD of 1.3 (assumed empirical value)
Renal clearance via GFR	By use of the equation below, three normal-distributed random variables were obtained: Hill coefficient = 15 ± 0.257, TM50 = 44.4 ± 1.04 weeks, and GFRmat = 266 ± 60.7 min−1 $\text{GFR}=((\frac{{\text{PMA}}^{\text{Hill}}}{{\text{TM}}_{50}^{\text{Hill}}+{\text{PMA}}^{\text{Hill}}}·(1-{\text{GFR}}_{\text{premat}}))+{\mathit{GFR}}_{\text{premat}})·{\text{Volume}}_{\text{Kidney}}·{\text{GFR}}_{\text{mat}}$	[70]
Active renal secretion via kidney P-gp transportera	Log-normal distribution and a geometric SD of 1.3	[62]
Gastric emptying time in the fasted state	Log-normal distribution with a geometric SD of 1.6 (based on data of more than 100 experimental gastric emptying profiles; data also used for the evaluation of the ontogeny)	[48, 73–75]
Gastric emptying time in the fed state	More than 100 experimental gastric emptying profiles that were obtained in healthy adults after ingestion of meals with an energy content of 593–1,051 kcal were used for the parameterisation of the gastric emptying time function of the Weibull type assuming a log-normal distribution of the parameters α and β, with geometric SDs of 1.74 in the case of α and 1.32 for β: $A(\text{time})=A_0\times {\text{e}}^{\frac{-\text{time}\mathit{\beta }}{\mathit{\alpha }}}$ The identical randomisation was done in children	[48]
Small intestinal transit time	Log-normal distribution with a geometric SD of 1.6	[76–82]
Large intestinal transit time	Log-normal distribution with a geometric SD of 1.6 based on literature data	[83, 84]
Effective surface area of intestinal sections	Log-normal distribution with a geometric SD of 1.6 (applies to all intestinal sections)	[85, 86]

^aRivaroxaban is a P-gp substrate

A amount of drug/volume of meal, A ₀ initial amount of drug/initial amount of meal, α optimised parameter depending on meal energy content (kcal), β optimisation parameter related to the fraction of solid components of the meal, CYP cytochrome P450, e exponent, GFR glomerular filtration rate, GFR _mat GFR after maturity, GFR _premat GFR during development, P-gp P-glycoprotein, PMA postmenstrual age, SD standard deviation, TM ₅₀ maturation half time