407-408 Does this speak to renal The Agency is insufficiency or to requested to speak augmented renal clearance to (ARC)? For ARC, how do we strengths/limitations better understand and of methods of predict this phenomenon? estimating The use of the Cockcroft- creatinine clearance Gault equation may be a for simulation less precise estimate of purposes and creatinine clearance in insights on certain circumstances such predicting as when renal function is individuals with not stable. Methods of ARC. estimated creatinine clearance should be clear & justified. Sponsor should consider whether using existing methods for estimation of creatinine clearance is an appropriate approach vs. an independent population PK derived approach for predicting the drug’s clearance.
407-408 Does this speak to renal insufficiency or to augmented renal clearance (ARC)? For ARC, how do we better understand and predict this phenomenon? The use of the Cockcroft- Gault equation may be a less precise estimate of creatinine clearance in certain circumstances such as when renal function is not stable. Methods of estimated creatinine clearance should be clear & justified. Sponsor should consider whether using existing methods for estimation of creatinine clearance is an appropriate approach vs. an independent population PK derived approach for predicting the drug’s clearance. The Agency is requested to speak to strengths/limitations of methods of estimating creatinine clearance for simulation purposes and insights on predicting individuals with ARC.
efpia_comments_draft_guideline_ema_pk-pd_antibacterial_final.docx