title: Distribution and serum concentration of sisomicin released from fibrin glue-sealed dacron graft in the rat and human.
abstract: We investigated whether or not fibrin glue (FG) used as a sealant in vascular prostheses to prevent leakage might be useful as a carrier of antibiotics for the prevention of local graft infection. Sisomicin (SISO) was incorporated into fibrin glue (SISO-FG) and evaluated as to its safety and pharmacokinetics. SISO (1.75 mg) -FG Dacron grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, and then the changes in SISO concentrations in the serum and in the tissue around the implantation sites were compared with those same sites in rats that had had intravenous injection of SISO (1.75 mg). The serum SISO concentrations were significantly lower in the SISO-FG Dacron graft group than they were in the intravenous injection group. However, until 4 h after implantation the SISO concentrations in the tissues around the implantation sites were significantly higher in the SISO-FG Dacron group than they were in the iv injection group, and the peak concentrations during that time were 5.8 times higher for the SISO-FG Dacron group than they were for the intravenous injection group. The ratio of the area under the tissue concentration time curve of SISO (AUC tissue) after implantation of the SISO-FG Dacron graft to that after intravenous injection of SISO was 13.08. Therefore, FG was considered to control the release of SISO into the serum and to maintain a high SISO concentration in the tissue around the implantation site. Clinically, SISO (45 mg) -FG was applied directly to the Dacron grafts implanted in 10 patients who underwent prosthetic vascular reconstruction. No graft infection was observed in any of the patients who received SISO-FG Dacron grafts. The mean serum concentration of SISO was 0.65+/-0.17 microg/mL after 1 h and 0.33+/- 0.21 microg/mL after 3 h. The results of these clinical applications are in close correlation with those of the animal experiment and suggest that FG is useful as a carrier of SISO, allowing its controlled release for the prevention of local infection.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Tsuruma-cho. Showa-ku, Nagoya, 466-8560, Japan. t-osada@med.nagoya-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Osada
authors.forename: K
authors.initials: K
authors.lastname: Yamamura
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: K
authors.initials: K
authors.lastname: Mizuno
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: T
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D005260:Female; D015718:Fibrin Tissue Adhesive; D006801:Humans; D008297:Male; D008875:Middle Aged; D011093:Polyethylene Terephthalates; D051381:Rats; D017207:Rats, Sprague-Dawley; D012853:Sisomicin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019737:Transplants
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D015718:Fibrin Tissue Adhesive; D011093:Polyethylene Terephthalates; D012853:Sisomicin