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A portal vein cannulation technique for drug discovery in mice

Abstract

One approach to understanding how orally administered drugs are absorbed and metabolized involves measuring compound concentrations in portal vein blood and in systemic circulation at various time points. In mice, blood samples are generally collected through terminal bleeding, a process that requires a large number of mice and is susceptible to variation between individuals. The authors developed a portal vein cannulation procedure for serial bleeding in the mouse, using a modified catheter containing a stainless steel stylet that is implanted directly in the portal vein. To demonstrate the technique, they orally administered two different compounds to mice and obtained blood samples from the tail vein and portal vein at different time points. They analyzed compound concentrations using liquid chromatography–tandem mass spectrometry. The technique refines existing methods for pharmacokinetic studies in the mouse and reduces the number of mice required.

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Figure 1: Concentrations (ng/ml) of compound A in mouse blood after oral administration.
Figure 2: Concentrations (ng/ml) of compound B in mouse blood after oral administration.
Figure 3

References

  1. Logan, C. in Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry) (eds. van de Waterbeemed, H., Lennernas, H. & Artursson, P.) 132–154 (Wiley-VCH, Weinheim, Germany, 2004).

    Book  Google Scholar 

  2. Schmidt, L.E. & Dalhoff, K. Food-drug interactions. Drugs 62, 1481–1502 (2002).

    Article  CAS  Google Scholar 

  3. Ward, K.W., Azzarano, L.M., Evans, C.A. & Smith, B.R. Apparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in rat. I. Investigation of potential experimental and mechanistic explanations. Xenobiotica 34, 353–366 (2004).

    Article  CAS  Google Scholar 

  4. Sasaki, K. et al. Improvement in the bioavailability of poorly absorbed glucyrrhizin via various non-vascular administration routes in rats. Int. J. Pharm. 265, 95–102 (2003).

    Article  CAS  Google Scholar 

  5. Konshi, Y., Hitomi, Y., Yoshida, M. & Yoshioka, E. Absorption and bioavailability of artepillin C in rats after oral administration. J. Agric. Food Chem. 53, 9928–9933 (2005).

    Article  Google Scholar 

  6. Lee, K.M., Muralidhara, S., White, C.A. & Bruckner, J.V. Mechanisms of the dose-dependent kinetics of trichloroethylene: oral bolus dosing of rats. Toxicol. Appl. Pharmacol. 164, 55–64 (2000).

    Article  CAS  Google Scholar 

  7. Kanazu, T., Okamura, N., Yamaguchi, Y., Baba, T. & Koike, M. Assessment of the hepatic and intestinal first-pass metabolism of midazolam in a CYP3A drug-drug interaction model rats. Xenobiotica 35, 305–317 (2005).

    Article  CAS  Google Scholar 

  8. van Dongen, J.J., Remie, R., Rensema, J.W. & van Wunnik, G.H. (eds) Manual of Microsurgery on the Laboratory Rat. Part 1: General Information and Experimental Techniques 213–222 (Elsevier, Amsterdam, 1990).

    Google Scholar 

  9. Russell, W.M.S. & Burch, R.L. The Principles of Humane Experimental Technique (Metheun & Co., London, 1959).

    Google Scholar 

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Acknowledgements

We thank Dr. Lotus Altholtz for her efforts in preparing this publication.

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Correspondence to Xiaolan Shen.

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The authors declare no competing financial interests.

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Shen, X., Yao, Z., Johnson, T. et al. A portal vein cannulation technique for drug discovery in mice. Lab Anim 37, 41–44 (2008). https://doi.org/10.1038/laban0108-41

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