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