“…A population PK model for midazolam in children was developed based on concentration-time data, to establish a pediatric covariate function for midazolam clearance. Next, we selected a range of drugs that are CYP3A substrates that are commonly prescribed in children, covering compounds prescribed for varying indications in different therapeutic areas, with oral or intravenous administration, and with different drug properties, i.e., alprazolam (14), atorvastatin (15), cisapride (16), domperidone (17), quinidine (18), sildenafil (19), simvastatin (20), solifenacin (21), sufentanil (22), sirolimus (23), tacrolimus (24), tamsulosin (25), and vincristine (26). Based on the drug properties of these CYP3A substrates, we used the framework of Calvier et al (7) to define which age the covariate function for midazolam can be used for accurate scaling of pediatric clearance of the CYP3A substrates from adult clearance values.…”