Using Prior Knowledge on Systems Through PBPK to Gain Further Insight into Routine Clinical Data on Trough Concentrations: The Case of Tacrolimus in Chronic Kidney Disease.

ABSTRACT:

Background

Routine therapeutic drug monitoring (TDM) relies heavily on measuring trough drug concentrations. Trough concentrations are affected not only by drug bioavailability and clearance, but also by various patient and disease factors and the volume of distribution. This often makes interpreting differences in drug exposure from trough data challenging. This study aimed to combine the advantages of top-down analysis of therapeutic drug monitoring data with bottom-up physiologically-based pharmacokinetic (PBPK) modeling to investigate the effect of declining renal function in chronic kidney disease (CKD) on the nonrenal intrinsic metabolic clearance ( CLint ) of tacrolimus as a case example.

Methods

Data on biochemistry, demographics, and kidney function, along with 1167

SUBMITTER: El-Khateeb E 

PROVIDER: S-EPMC10635338 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature