새로운 경구용 세팔로스포린류의 물리화학적 성질 및 분해특성

• 영문명: Physicochemical Properties and Degradation of New Oral Cephalosporins
• 발행기관: 대한약학회
• 저자명: 나성범(Sung Bum La) 김완주(Wan Joo Kim) 지웅길(Ung Kil Jee)
• 간행물 정보: 『약학회지』제38권 제2호 (1994년), 123~130쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1994.04.30

영문 초록

Physicochemical properties and hydrolysis kinetics of new some oral cephalosporins were examined in buttered solution and human plasma or rat liver homogenate. The test cephalosporins were 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamidol-3-[4-(2-pyridyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN1), 7-E(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyllthiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN2), pivaloyloxymethyl-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylate (CENlP), and pivaloyloxymethyl-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido1-3-[4-(2-pyrimidyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylate (CEN2P). The partition coefficient(Ko/w) of CEN1P, CEN2P were higher than those of CEN1, CEN2. The calculated pKa values of CEN1, CEN2, CEN1P, and CEN2P were 7.09, 7.75, 4.92, and 5.39, respectively. The hydrolysis of CEN1P and CEN2P were not depend on the composition of pH of the test medium except weak alkaline buffered solution (pH 8.00). CEN1 and CEN2 were very stable in pH 6.80 and 8.00 buffer solutions. CEN1P and CEN2P were rapidly deesterified to CEN1 and CEN2 in human plasma and in rat liver homogenate. Half-lives(t1/2) of CEN1 and CEN2 were 3.49 and 4.93 hr in human plasma, 1.47 and 1.26 hr in rat liver homogenate, respectively.

키워드

Oral cephalosporins Ko/w pKa Hydrolysis Artificial gastric juice Artificial intestinal juice Human plasma Rat liver homogenate.