PK Analysis in Toxicokinetic Studies
What is the most appropriate way to naively pool plasma
concentrations for noncompartmental pharmacokinetic analysis
of data obtained in routine toxicokinetic studies in
rodents? Typically, many individual plasma concentrations
are below the limit of quantification (BQL) at this stage of
drug development.
A typical study design is as follows: 6 rats per sex per
dose are divided into two sets of 3. A maximum of 3 blood
samples is obtained from each set on an alternating basis.
Blood sampling times are 0.5, 1, 2, 4, 6 and 8 hr after
dosing.
Is it appropriate to substitute missing BQL values with
zero, obtain the mean, then determine the pharmacokinetic
parameters? Is there a superior method for summarizing the
data? Should NONMEM be used? I look forward to your
comments.
Sincerely, Derek A. Ganes, Ph.D.