인터루킨-2의 제제설계를 위한 체내 동태학적 연구

• 영문명: Pharmacokinetic Preformulation Study of rH IL-2
• 발행기관: 대한약학회
• 저자명: 서민석(Min Seok Seo) 심창구(Chang Koo Shim) 권종범(Jong Bum Kwon) 나도선(Do Sun Na) 이선복(Sun Bok Lee) 함경수(Kyung Soo Hahm) 한문희(Moon Hi Han)
• 간행물 정보: 『약학회지』제34권 제4호 (1990년), 238~243쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1990.08.28

영문 초록

Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) were studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rH IL-2 in the dose range of 6,400-40,000U/kg. But at the dose of 1,600,000U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the volume of distribution (Vdss) and total body clearance (CLt) were 45-75ml/kg and 1-2ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of alpha-inteferon. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

키워드

Interleukin-2 pharmacokinetics bioavailability intravenous hepatoportal oral intraperitoneal intransal administration.