Reporting bugs in the calculation of PK parameters in steady-state

[diabloyg]

Hi, I did several tests and found that there are several issues in the calculation of steady-state PK parameters (doseType = "ss"):

1. The time t in the calculation of AUC0-t and AUMC0-t is based on the closet time to the Tau, instead of the largest one. For example, if I had sample with time of 72 h and 192 h (24 h after scheduled 168 h), and I define Tau as 168 h, then the AUC0-t is calculated as AUC0-192h. However, if the patients had a unschuduled visit at 150 h (-14 h compared with Tau which is the closest), then the AUC0-t is calculated as AUC 0-150h. It could be better to always use the largest time provided to calculate AUC0-t and AUMC0-t.

2. The AUC or AUMC0-tau is based on Tau and AUC or AUMC 0-t through extrapolation. However, if the time point of last sample is greater than Tau (and is closest to Tau), then the AUC or AUMC0-Tau is equal to AUC or AUMC0-t, instead of intrapolation based on AUC or AUMC0-t.

It seemed that only the extrapolation from time point smaller the Tau worked well. In the former scenario where the last time point is greater than Tau (and is closest to Tau), the calculation of MRT as well as CLss would be not accurate, since the AUC0-tau and AUMC0-tau are not appropriately calculated, although AUC0-tau itself could be alternatively calculated using option AUCTimeRange.