title: Pharmacokinetics of dicrofenac after its intrarectal and intracolostomal administration to rabbits with rectal resection or colostoma construction.
abstract: We investigated the pharmacokinetics of diclofenac, one of the important analgesics in palliative care, after its intrarectal and intracolostomal administration to rabbits with rectal resection or colostoma construction. In rectal-resected rabbits, its bioavailability after rectal administration was significantly lower than that in normal rabbits, and furthermore that after intracolostomal administration was significantly lower than that in rectal-resected rabbits. This decreased bioavailability in rabbits with rectal resection and colostoma construction was thought to be due to the increased first-pass effect. With increase in the dose up to 1.5-fold, the plasma concentrations in both rectal-resected and colostoma-constructed rabbits increased to the normal rabbit level. These results indicate that the bioavailability of diclofenac sodium after its rectal and intracolostomal administration decreases, and that an increased dose can restore the decreased plasma concentration. There was no difference in the plasma concentration with diclofenac sodium suppositories between administration into the normal rectum and the remaining rectum following colostoma construction, and the remaining rectum was found to be a useful administration route for suppositories. Therefore, it was indicated that when administering diclofenac sodium suppositories to rectal-resected and colostoma-constructed patients, the dose should be increased, because the pharmacokinetics of diclofenac was similar in rabbits and human.
authors.affiliation: Department of Environmental Biochemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. nagasawa@mb.kyoto-phu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Nagasawa
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Takara
authors.forename: N
authors.initials: N
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003125:Colostomy; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits; D012007:Rectum / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac