(M1030-03-20) Development and Implementation of a Ferret Venous Catheterization Model for Pharmacokinetic Studies

Purpose: The ferret (Mustela putorius furo) is an indispensable experimental animal model in the fields of influenza virology, respiratory diseases, and vaccine development. However, its unique physiological and anatomical characteristics pose significant challenges for venous blood sampling. The peripheral blood vessels, such as the saphenous and caudal veins, are extremely narrow (0.3-0.5mm in diameter), and the subcutaneous fat layer combined with thick epidermal structures complicates visualization. Additionally, ferrets exhibit a more pronounced stress-induced vascular contraction response compared to rodents, resulting in a lower success rate of traditional blood sampling.

Methods: To overcome these challenges, we have established a novel venous catheterization model for ferrets, tailored for pharmacokinetic (PK) studies requiring serial blood sampling. This innovative technique, reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of WuXi AppTec, employs the Venous Access-Port (VAP) method. The procedure involves intubation surgery from the jugular vein to the vena cava, facilitating serial venous blood sampling via an indwelling catheter.

Results: Our newly established catheter sampling method has shown a significant reduction in interindividual variability, evidenced by lower standard deviations across key PK parameters for Palamivir and Arepitine compared to traditional puncture sampling methods. For example, the mean and standard deviation of clearance (Cl) for Peramivir in WuXi AppTec and references was 4.10±0.245 vs. 4.97±3.98 mL/min/kg, respectively, T_1/2 was 3.09±0.754 vs. 3.65±0.320h, and the volume of distribution at steady state (Vd_ss) was 0.385±0.0706 vs. 0.355±0.306L/kg following a 10 mg/kg Palamivir intravenous single bolus dose.

Conclusion: These findings suggest that the intravenous intubation model based on subcutaneous VAP technology provides a more precise, reliable, and cost-effective approach to venous blood sampling in ferrets. This advancement not only improves the quality of experimental data but also aligns with ethical considerations by reducing animal stress.

References: [1] Powers L V., Perpiñán D. Basic Anatomy, Physiology, and Husbandry of Ferrets[M/OL]//Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. Fourth Edi. Elsevier, 2020. https://dx.doi.org/10.1016/B978-0-323-48435-0.00001-0. DOI:10.1016/B978-0-323-48435-0.00001-0.
[2] Sweet C, Jakeman K J, Bush K, et al. Oral administration of cyclopentane neuraminidase inhibitors protects ferrets against influenza virus infection[J/OL]. Antimicrobial Agents and Chemotherapy, 2002, 46(4): 996-1004. DOI:10.1128/AAC.46.4.996-1004.2002.
[3] Huskey S E W, Dean B J, Bakhtiar R, et al. Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets[J/OL]. Drug Metabolism and Disposition, 2003, 31(6): 785-791.