Effect of viscous additives on drug absorption from the liver surface in rats using phenol red as a model.
The purpose of this study is to obtain information that can be used to improve controlled release and residence time of drugs on the liver surface. Using carboxymethylcellulose sodium salt (CMC-Na) and polyvinyl alcohol (PVA), we examined the effect of viscous formulations on the absorption of phenol red as a model. In the presence of 3% CMC-Na or 15% PVA, the maximum plasma concentration of phenol red decreased after application to the rat liver surface using a cylindrical glass cell. The absorption ratios in 6 h calculated from the remaining amount of phenol red in the glass cell were 68.6, 60.5 and 48.7% (control: 73.1%) in the presence of 1 or 3% CMC-Na and 15% PVA, respectively. As a result of the reduction in the absorption ratio, the amount of phenol red excreted into the bile and urine in 6 h was decreased by the addition of the viscous additives. The decrease in absorption rate was characterized by a pharmacokinetic analysis of the plasma concentration profile. The change in absorption rate differed between the viscous additives, reflecting the result of the in vitro release experiment. Accordingly, the possibility that the drug absorption rate from the liver surface can be altered by viscous additives was suggested to have a promising prospect for therapeutic use.
Nishida
K
K
School of Pharmaceutical Sciences, Nagasaki University, Nagasaki, Japan. koyo-n@net.nagasaki-u.ac.jp
Nakakoga
Y
Y
Sato
N
N
Kawakami
S
S
Mukai
T
T
Sasaki
H
H
Sakaeda
T
T
Nakamura
J
J
D000042:Absorption; D000818:Animals; D001646:Bile / Q000378:metabolism; D001825:Body Fluid Compartments; D002021:Buffers; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008567:Membranes, Artificial; D008954:Models, Biological; D010539:Permeability; D010637:Phenolsulfonphthalein / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011142:Polyvinyl Alcohol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014783:Viscosity
D002021:Buffers; D003692:Delayed-Action Preparations; D005079:Excipients; D007202:Indicators and Reagents; D008567:Membranes, Artificial; D011142:Polyvinyl Alcohol; D010637:Phenolsulfonphthalein; D002266:Carboxymethylcellulose Sodium