The study was performed without external funding.
Kosman V.M. , Karlina M.V. Retrospective of pharmacokinetic parameters variability in dependence on biological species and number of individuals in the experimental group. Laboratory Animals for Science. 2023; 1. https://doi.org/10.57034/2618723X-2023-01-06
Determination of pharmacokinetic parameters in pharmacokinetic (PK) and toxicokinetic (TK) studies is a mandatory component of medicinal products preclinical study. One of the key points of such experimental studies planning is the test system and group size choice, the minimum size is regulated by normative documents. The group size increasing is expected to reduce the variability of obtained data.
The purpose of the work was to identify possible patterns of variability of PK parameters depending on the species and the number of individuals (n) in the experimental group to further justify the group size during PK and/or TK studies.
A retrospective array of own experimental data on variability coefficients (CV,%) of the main pharmacokinetic parameters (Cmax, Tmax, AUC0-t, AUC0-∞, MRT and T1/2) was formed included data obtained in various laboratory animals (rats, rabbits, cats, dogs, dwarf pigs) and human (as examples of studies with large n values), routes of administration (oral/intragastric, intravenous, intramuscular, vaginal, intranasal, intraperitoneal, cutaneous, endotracheal, rectal) and the number of individuals in the group (3–12 for laboratory animals and 8–30 for volunteers), data grouping and statistical processing were performed.
The greatest variability in Cmax, Tmax, AUC0-t, AUC0-∞ parameters, regardless of species and routes of administration, was identified for the most numerous groups (with more than 18 individuals).
Retrospective analysis of the accumulated data did not justify the advantages of a particular species as a test system, as well as recommend increasing the group size to obtain more homogeneous data on PK parameters.
The regulatory recommended number of animals (minimum 6 in the whole PK curve from one individual, minimum 5 in the animal-point design and minimum 4 males and 4 females in the TK studies) should be considered sufficient in preclinical PK/TK studies of medicinal products for human use. The increase in the number of animals in the experimental groups can be justified when studying the PK of veterinary drugs in the target animal’s species, since it will allow taking into account the individual characteristics more fully.
The authors declare no conflict of interest.
V.M. Kosman — idea, data collection and analysis, manuscript text and illustrations preparing.
M.V. Karlina — result discussion, critical manuscript text revision.
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