PK/PD Model for a Biomarker of Kidney Function
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*Joseph F Boucher, Pfizer Animal Health 

Keywords: pharmacokinetic, pharmacodynamic, adverse effect, mixed effect model

Certain classes of drugs can have an adverse effect on kidney function and can result in increases in the biomarkers creatinine and BUN. In a clinical trial in dogs for an NCE, increases to both creatinine and BUN were observed relative to the control group. A model was developed to try to identify risk factors associated with the increased creatinine. Based on the proportion of creatinine measurements that were above the reference range a logistic regression model was used to identify associated factors. Two specific questions that were of particular interest were: 1. Does long term use increase the risk of adverse creatinine levels? and 2. Are higher plasma drug concentrations related to an increase in the risk of adverse creatinine levels? Additionally, an attempt was made to identify other covariates that helped to explain the increase in creatinine.