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Antimicrobial Agents and Chemotherapy, March 2001, p. 917-921, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.917-921.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pharmacokinetics of a New Parenteral Oligosaccharide Antibiotic, SCH27899 (Ziracin), in Healthy Subjects

Osamu Kozawa,1 Toshihiko Uematsu,1,* Hiroyuki Matsuno,1 Masayuki Niwa,1 Ken-Ichi Kohno,2 Asakazu Kawato,3 Kazuyoshi Takahashi,3 Satoru Nagashima,2 and Mitsutaka Kanamaru2

Department of Pharmacology, Gifu University School of Medicine, Gifu 500-8705,1 Shitoro Clinic, Hamamatsu 432-8066,2 and R & D Division, Clinical Development Department, Schering-Plough KK, Osaka 541-0046,3 Japan

Received 13 April 2000/Returned for modification 8 October 2000/Accepted 26 December 2000

The pharmacokinetic properties of an everninomicin antibiotic (SCH27899; Ziracin) were studied with healthy Japanese male volunteers by single (1, 3, 6, and 9 mg/kg of body weight) and multiple 60-min intravenous infusions (3, 6, and 9 mg/kg once daily for 10 consecutive days following a 2-day interval after the initial dose). At single doses the peak serum concentration and the area under the serum concentration-time curve linearly increased with the dose. While total body clearance (CL; 31.2 to 45.6 ml/kg/h) and percent cumulative urinary recovery as unchanged drug (4.9 to 7.1%) were rather constant irrespective of doses, the terminal half-life of gamma  phase (t1/2gamma ; 14.2 to 19.6 h) were slightly prolonged at the higher two doses compared with the lower two doses. With repeated doses of SCH27899, a statistically significant decrease and increase were found in CL and t1/2gamma of about 36 and 21%, respectively, although these changes may be clinically irrelevant. The most commonly reported adverse events were local reactions such as erythema, pain, and palpable venous cord of mild to moderate degree around the injection site, which could be managed by changing the injection sites.


* Corresponding author. Mailing address: Department of Pharmacology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500, Japan. Phone: 81-58-267-2231. Fax: 81-58-267-2959. E-mail: uematsu{at}cc.gifu-u.ac.jp.


Antimicrobial Agents and Chemotherapy, March 2001, p. 917-921, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.917-921.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.