세팔로스포린 3''-퀴놀론의 물리화학적 성질, 안정성 및 체내약물동태

• 영문명: Physicochemical Properties, Stabilities and Pharmacokinetics of Cephalosporin 3''-Quinolone Dithiocarbamate
• 발행기관: 대한약학회
• 저자명: 나성범(Sung Bum La) 공재양(Jae Yang Kong) 김완주(Wan Joo Kim) 지웅길(Ung Kil Jee)
• 간행물 정보: 『약학회지』제37권 제6호 (1993년), 638~646쪽, 전체 9쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1993.12.30

영문 초록

A cephalosporin with an aminothiazolylmethoxyimino-type side chain at the 7 position and bicyclic quinolone dithicarbamate at the 3'' position was synthesized. It has broad and potent antivacterial activity in vitro. The antibacterial spectrum reflects contributions of both the cephalosporin moiety and the quinolone moiety. Thus, this compound was named DACD implying a dualaction cephalosporin derivative. In this paper, the physicochemical properties (lipid-water partition, pKa), stability and pharmacokinetics of DACD were determined and compared with cefotaxime 3''-norfloxacin dithiocarbamate (CENO). Stability tests were studied in pH 1.20, 6.80 and 8.00 buffers and in the presence of AB type human plasma, rat liver homogenate and its beta-lactamase. The pharmacokinetic parameters of DACD were evaluated in mice after a single intravenous dose of 40mg/kg. The results are as follows. The lipid-water partition coefficient of DACD was higher than that of CENO. The calculated pKa values of CENO and DACD, were 6.82 +/- 0.03, 7.53 +/- 0.21, respectively. In the hydrolysis test, half-lives (t1/2) of CENO and DACD was 66.0 hr and 80.0 hr in pH 6.80 buffer, 190 hr and 91.4 hr in pH 8.00 buffer. CENO and DACD were rapidly hydrolyzed in human plasma and in rat liver homogenate. Half-lives (t1/2) of CENO and DACD were 1.29 hr and 1.15 hr in hyman plasma, 0.62 hr and 0.71 hr rat liver homogenate. In beta-lactamase stability test, CENO and DACD were very stable to the beta-lactamases obtained from three different strains. Half-life (t1/2) and areas under the curve (AUC) in mice were 2.33 hr and 15.97 (mg.h/l), respectively.

키워드

Dual-action cephalosporins DACD pKa lipid-water partition coefficient stability test artificial gastric juice artifical intestinal juice human plasma rat liver homogenate beta-lactmase stability pharmacokinetics.