Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human

Takashi Osada, Keiko Yamamura, Kohji Yano, Katsuhiro Fujimoto, Keisuke Mizuno, Tsunehisa Sakurai, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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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 μg/mL after 1 h and 0.33 ± 0.21 μg/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. (C) 2000 John Wiley and Sons, Inc.

Original languageEnglish
Pages (from-to)53-57
Number of pages5
JournalJournal of Biomedical Materials Research
Volume52
Issue number1
DOIs
Publication statusPublished - 01-08-2000
Externally publishedYes

Fingerprint

Sisomicin
Fibrin Tissue Adhesive
Polyethylene Terephthalates
Glues
Grafts
Rats
Tissue
Prosthetics
Pharmacokinetics
Sealants
Antibiotics

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering

Cite this

Osada, Takashi ; Yamamura, Keiko ; Yano, Kohji ; Fujimoto, Katsuhiro ; Mizuno, Keisuke ; Sakurai, Tsunehisa ; Nabeshima, Toshitaka. / Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human. In: Journal of Biomedical Materials Research. 2000 ; Vol. 52, No. 1. pp. 53-57.
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Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human. / Osada, Takashi; Yamamura, Keiko; Yano, Kohji; Fujimoto, Katsuhiro; Mizuno, Keisuke; Sakurai, Tsunehisa; Nabeshima, Toshitaka.

In: Journal of Biomedical Materials Research, Vol. 52, No. 1, 01.08.2000, p. 53-57.

Research output: Contribution to journalArticle

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T1 - Distribution and serum concentration of sisomicin released from fibrin glue-sealed Dacron graft in the rat and human

AU - Osada, Takashi

AU - Yamamura, Keiko

AU - Yano, Kohji

AU - Fujimoto, Katsuhiro

AU - Mizuno, Keisuke

AU - Sakurai, Tsunehisa

AU - Nabeshima, Toshitaka

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