PK Sample Collection in Control Groups for GLP Studies
Yes, PK samples should be collected in control (vehicle-treated) groups in GLP studies to enable proper interpretation of drug exposure-response relationships and to account for baseline variability in the biological matrix.
Rationale for Control Group PK Sampling
Control group sampling is essential for establishing baseline measurements and ensuring valid PK/PD modeling. 1 All PK/PD studies are required to include a vehicle-treated control group along with drug-treated groups to properly interpret pharmacological effects and exposure-response relationships. 1
Key Considerations for Control Group Sampling
Baseline establishment: Control samples allow determination of endogenous concentrations of analytes that may be present in the biological matrix, which is critical when the test compound or related substances exist naturally in plasma or tissues. 2
Study design integrity: When PK and PD readouts cannot be obtained from the same animals (due to sample volume restrictions or perturbation of PD caused by PK sampling), PK sampling should be done in a satellite group of animals matched in all aspects of study design including sex, strain, species, dose administration, sample times, disease state, and operator to minimize variability. 1
Matrix effects and assay validation: Control samples are necessary to assess selectivity of analytical methods and to prepare quality control (QC) samples in the biological matrix, particularly when dealing with endogenous compounds. 2
Practical Implementation
Sample timing: Control group samples should be collected at the same timepoints as drug-treated groups to enable direct comparison and proper statistical analysis. 1
Documentation requirements: Precise recording of sampling times using calendar time (month, day, hours, minutes) is essential for both control and treated groups. 1
Preinfusion/baseline samples: Include preinfusion samples to establish baseline levels before any intervention, which is particularly important when compounds may accumulate or when endogenous levels vary. 1, 3
Common Pitfalls to Avoid
Ignoring below-limit-of-quantification (BLQ) data: Report all measurements including those below the limit of quantification rather than discarding them, as ignoring BLQ data may bias individual estimates. 1, 4
Inadequate control matching: Ensure control animals are matched in all relevant parameters to drug-treated groups to minimize confounding variability. 1
Insufficient validation: Commercial immunoassay kits adapted for GLP-compliant PK studies require systematic evaluation and validation to establish selectivity, sensitivity, linearity, accuracy, precision, and stability. 2