Tissue distribution and metabolism of drugs V: effect of secretin and pancreozymin on drug transport in rabbit pancreas.

The effect of secretin and pancreozymin on the tissue distribution and penetration of drugs in the rabbit pancreas was studied to clarify hormonally regulated drug distribution. Drugs with high liquid solubility were distributed easily within the pancreas even during secretin or pancreozymin treatment, and these hormones had little effect on drug distribution from the blood to the pancreas. However, secretin increased the concentration ratio of dimethadione in the pancreatic juice (J) to plasma unbound dimethadione (Pf), probably because the pancreatic juice during secretin infusion is alkaline relative to the control. Secretin had no effect on the J/Pf of isonicotinamide and sulfanilamide. Secretin decreased the J/Pf of drugs with low lipophilicity or large molecular weight because the penetration rates of these drugs from cell water to pancreatic juice were not rapid enough to reach equilibrium. Pancreozymin was unable to change the J/Pf of any drug tested. These results suggest that the barrier between the blood and the pancreas or the barrier between the pancreas and the pancreatic juice is unchanged by secretin or pancreozymin.