Rectal absorption of E-2078 (dynorphin analogue peptide) in rats.
The plasma levels in rats of a dynorphin analogue peptide (E-2078) after rectal administration have been studied. The bioavailabilities of E-2078 after rectal administration, subcutaneous injection, intramuscular injection, and oral administration were 21.6, 67.8, 67.1, 0.7%, respectively. The effect of dose, pH, osmolarity and viscosity on the rectal absorption of E-2078 were studied. A sigmoid relationship between the dose and the AUC was observed on rectal administration, while there was a linear relationship on intramuscular administration. The AUC was increased in acidic solution and highly viscous solution. The osmolarity did not affect the absorption of E-2078. In microscopic studies, E-2078 caused little or no damage to the rectal mucosa in rats.
Murahashi
N
N
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Kato
A
A
Koyama
N
N
Watanabe
S
S
Yuzuriha
T
T
Miyake
Y
Y
D000284:Administration, Oral; D000285:Administration, Rectal; D000595:Amino Acid Sequence; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D004399:Dynorphins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007267:Injections; D007408:Intestinal Absorption; D008297:Male; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014783:Viscosity
D000700:Analgesics; D010446:Peptide Fragments; C061285:E 2078; D004399:Dynorphins