title: Bioavailability of a morphine suppository is increased after intracolostomal administration in colostoma-constructed rabbits.
abstract: This study was performed to assess the pharmacokinetics of morphine and its major metabolites after its rectal or colostomal administration in rectal-resected (ROP) or colostoma-constructed (SOP) rabbits, respectively. The pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and M6G in normal rabbits appeared to be similar to those in human, judging from their plasma concentration-time profiles and the susceptibility of morphine to first-pass metabolism. In SOP, but not ROP, rabbits, the plasma concentrations of morphine, M3G and M6G were significantly increased compared with those in normal rabbits. The AUC of morphine and its metabolites, and the F value of the former in the SOP group were greater than those in the control group, while the elimination half-life (t(1/2)) values were comparable in the two groups. In addition, the disposition of morphine and its metabolites after intravenous (i.v.) administration to SOP rabbits was almost the same as that in normal rabbits, suggesting that an increase in the rate of absorption of morphine in SOP rabbits was not due to inflammation at the absorption site caused by operation, but probably due to its increased solubility in loose stools. Therefore, great attention should be paid when morphine suppositories are intracolostomally administered to colostoma-constructed patients.
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: Kazuki
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kintsuji
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Nagai
authors.forename: Sadaki
authors.initials: S
authors.lastname: Fujimoto
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D003125:Colostomy; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D013488:Suppositories
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D013488:Suppositories; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide