Re: flip-flop without absorption information?

Dear Niurys, It would be down to distributional assumptions in that case. For example if you have a very strong predictor (covariate) of either elimination or absorption rate (but not both) - data could be informative to discriminate between flip-flop or not. Had your therapeutic been IgG monoclonal antibody, albumin wold have been a predictor of the absolute CL that with a larger number of subjects may allow to discriminate (especially if a mix of both healthy, and patients with higher inflammation level and thereby lower albumin -> higher CL). On the other hand, for example body weight would not be helpful in this regard. Even if body weight would have an effect on CL and V, it would not have a major impact on terminal elimination (and in addition one could have a concern on body weight also affecting the absorption rate). So you would need both the mechanistic knowledge on the covariate, for your therapeutic peptide in the RA population, and it would need to be a strong effect in sufficient number of subjects. On such obvious covariate would be different routes of administration, where nobody would question the mechanistic knowledge on that SC has a slower absorption that IV :>) In liu of IV dosing this becomes a more challenging task, however. Best wishes Jakob