Hi,
I'm reviewing the toxicokinetic report provided by CRO, I got a little confused regarding data interpretation so that I ask some questions here.
1. Dose proportionality: As some biologics (mAb, ADC) developed significant ADA after multiple doses which might reduce exposure after multiple doses, should I evaluate dose proportionality based on the exposures from first dose only ?
2. AUCtau
My understanding is AUCtau should not be greater than AUCinf_obs. However, the dataset at terminal phase (336 h and 504h) were found below LLOQ , 168h was the last measurable timepoint. BQL rules were specified to treat all concentration below LLOQ as zero.
I'm afraid that the result of AUCtau was overestimated since the value was greater than AUCinf_obs. Should I consider AUC0-t to evaluate accumulation after multiple doses ?
3. MRTinf_obs
Due to AUCtau being greater than AUCinf_obs, the MRTinf_obs was reported as a negative value and also Vss couldn't be reported. Is there any other way to obtain CLss?
Thank you in advance for your help.
Best Regards,
