Pharmacokinetics of intravenous and oral metformin and r,s-verapamil in Sinclair, Hanford, Yucatan and Göttingen minipigs


Patel, N.J., Yumibe, N., Ruterbories, K., Huang, N., Burns, L., Tan, J., White, D., Liu, J., Brocksmith, D., Bouchard, G.F., Stricker-Krongrad, A.


Oral and intravenous pharmacokinetic (PK) studies were conducted in four different minipig strains: Sinclair, Yucatan, Hanford and Göttingen after administration of metformin or R,S-verapamil (R,S-VER). Results: The results indicated that the PK of metformin was similar between all minipig strains, except for the Göttingen which
had higher plasma clearance. The plasma clearance of both (+)-(R)- and (−)-(S)- VER was significantly lower in Sinclair compared with the clearance in other strains. The (+)-(R)-NOR to R,S-VER ratio was significantly higher in the Sinclair. There was a preferential conversion of R,S-VER to (+)-(R)-NOR over (−)-(S)-NOR in all minipig strains. Conclusion: This work highlights the importance of considering the impact of metabolic and dispositional differences in minipig strains when conducting PK studies.

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