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With the emergence of new tools like physiologically based PK modeling, the decision to conduct an in vivo study can be made with much more confidence. This review provides a comprehensive overview of various factors that need to be considered in designing OC DDI studies and recommends PK-based DDI studies with PK end points as adequate measures to establish clinical drug interaction and measurement of PD end points when there is basis for PD interaction.Maternal opioid use disorder increased 4-fold from 1999 to 2014 and is associat