Proposed new addition to 3Rs for ethical and humane use of rats in pharmacokinetic studies--'Recycle'.
The great emphasis on ethical and humane treatment of animals in biomedical research has culminated in the promulgation of the rule of 3Rs - Replacement, Reduction, and Refinement. We have proposed an addition to the 3Rs - a fourth R for Recycling the animal. In drug discovery single-dose pharmacokinetic studies in rats, each animal is generally used only once and then euthanized. A reduction in the number of rats used in this high-throughput era can be readily implemented by reusing animals, just as larger animals are reused in multiple pharmacokinetic studies, consequently reducing the overall number of animal lives sacrificed in research. We provide evidence here for the reproducibility of pharmaco-kinetic studies of tolbutamide and fluconazole, used as test compounds, in rats receiving once-weekly oral and intravenous doses for 4 weeks, proving that recycling rats for multiple single low-dose pharmacokinetic studies is a viable option.
Balani
Suresh K
SK
Drug Metabolism and Pharmacokinetics, Non-Clinical Development Sciences, Millennium Pharmaceuticals, The Takeda Oncology Company, 35 Landsdowne Street, Cambridge, Massachusetts 02139, USA. suresh.balani@mpi.com
Lu
Chuang
C
Cardoza
Kym
K
Berg
Cicely
C
Zhang
Ji
J
Lee
Frank W
FW
D032761:Animal Experimentation / Q000941:ethics*; D000827:Animal Welfare / Q000941:ethics*; D000818:Animals; D015725:Fluconazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014044:Tolbutamide / Q000008:administration & dosage / Q000493:pharmacokinetics
D015725:Fluconazole; D014044:Tolbutamide