Effect of instillation method on the absorption of phenolsulphonphthalein as a model drug from the liver and small intestinal serosal surface in rats.
We have examined the effect of the instillation method on the absorption of a drug from the liver and the small intestinal serosal surface in rats. We performed continuous microinstillation via an infusion pump and bolus instillation via a syringe, using phenolsulphonphthalein (phenol red) as the model drug. After continuous microinstillation of phenolsulphonphthalein 2.35 mg in 235 microL for 5 min on the liver and small intestinal serosal surface in rats, the AUC (area under the curve) of the plasma concentration profile up to 60 min was significantly higher compared with bolus instillation. A similar trend was observed after continuous microinstillation of phenolsulphonphthalein 2.35 mg in 117.5 microL for 2.5 min. The calculated absorption rate constants (Ka) after continuous microinstillation of phenolsulphonphthalein based on a two-compartment model with first-order absorption were higher than those after bolus instillation on the liver and small intestinal serosal surface at either instillation concentration. Moreover, Ka was increased after continuous microinstillation of 2.35 mg in 117.5 microL at either instillation site. Instillation of phenolsulphonphthalein on the liver surface resulted in a 1.2- to 2.3-fold higher Ka compared with the small intestinal serosal surface. This tendency was marked after continuous microinstillation of 2.35 mg in 117.5 microL. In conclusion, absorption could be enhanced by instilling a small amount of drug solution on the liver surface gradually and continuously, suggesting a promising approach for instillation site-selective drug delivery in the peritoneal cavity.
Nishida
K
K
School of Pharmaceutical Sciences, Nagasaki University, Japan. koyo-n@net.nagasaki-u.ac.jp
Yoshida
Y
Y
Mukai
T
T
Kawakami
S
S
Sakaeda
T
T
Nakashima
M
M
Sasaki
H
H
Nakamura
J
J
D000465:Algorithms; D000818:Animals; D004396:Coloring Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007267:Injections; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010637:Phenolsulfonphthalein / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D004396:Coloring Agents; D010637:Phenolsulfonphthalein