Rectal absorption enhancement of cefoxitin and desglycinamide arginine vasopressin by sodium tauro-24,25-dihydrofusidate in conscious rats.
The effects of sodium tauro-24,25-dihydrofusidate (STDHF), an enhancer of nasal insulin absorption, on the rectal absorption of cefoxitin and desglycinamide arginine vasopressin (DGAVP) were evaluated in the rat. Cefoxitin and DGAVP proved to be poorly absorbed rectally without STDHF, but their bioavailability was considerably increased by STDHF in concentrations of 0.15 to 8% w/v. Both rectal infusion and rectal bolus delivery resulted in complete cefoxitin absorption at 4% w/v of STDHF. Delivery rate appeared to be an important factor in the effect of 4% w/v of STDHF on DGAVP bioavailability; on infusion a mean DGAVP bioavailability (+/- S.D.) of 47 +/- 12% was obtained, whereas after bolus delivery it amounted to 27 +/- 6%. For both compounds the effect of STDHF was significant at 0.5% w/v. It is concluded that STDHF is capable of actively enhancing the rectal absorption of poorly absorbed drugs, including small peptides.
van Hoogdalem
E J
EJ
Division of Pharmacology, State University of Leiden, Sylvius Laboratories, The Netherlands.
Heijligers-Feijen
C D
CD
Mathôt
R A
RA
Wackwitz
A T
AT
van Bree
J B
JB
Verhoef
J C
JC
de Boer
A G
AG
Breimer
D D
DD
D000818:Animals; D001127:Arginine Vasopressin / Q000493:pharmacokinetics / Q000031:analogs & derivatives; D001682:Biological Availability; D002440:Cefoxitin / Q000493:pharmacokinetics*; D005672:Fusidic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000378:metabolism; D013268:Stimulation, Chemical
D001127:Arginine Vasopressin; C015119:argipressin, des-GlyNH2(9)-; D005672:Fusidic Acid; C053824:tauro-24,25-dihydrofusidate; D002440:Cefoxitin