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. 2020 May 13;11:587. doi: 10.3389/fphar.2020.00587

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Copyright © 2020 Smits, Annaert, Van Cruchten and Allegaert

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Output of a sensitivity analysis for midazolam clearance (CL) in neonates, illustrating the model-predicted impact of changes in Michaelis–Menten constant (K_m) and/or maximum reaction rate (V_max) describing the intrinsic formation CL of 1-OH midazolam by CYP3A4. The ‘dashed' circle represents the V_max/K_m values at normothermia, while the yellow arrow indicates a plausible change in V_max (rather than K_m) under conditions of hypothermia.