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신규 백금착물 항암제 KBP31705-C127 , KBP30603-901 의 Clsplatn 및 Carboplatin 과의 약동력학적 동태 비교
정인숙(In Sook Jung),이주선(Ju Seon Lee),허수정(Soo Jung Huh),김진숙(Jin Sook Kim),진창배(Chang Bae Jin),김동현(Dong Hyun KIm),김명수(Myung Soo Kim),박경수(Kyung Su Park),손연수(Youn Soo Sohn),백형기(Hyoung Gee Back),조양하(Yang Ha C 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.4
The present study examined pharmacokinetic profiles of KBP31705-C127 and KBP30603-901, new platinum coordination complexes synthesized as anticancer candidates, in comparison with two well-known platinum-containing anticancer agents, cisplatin and carboplatin in rats. Under sodium pentobarbital anesthesia of male Sprague-Dawley rats, urinary bladder, and femoral artery and vein were catheterized for urine collection, blood sampling and drug injection, respectively. Following i.v, administration of cisplatin (2 ㎎/㎏), KBP31705-C127 (2 ㎎/㎏), carboplatin (20 ㎎/㎏) or KBP30603-901 (20 ㎎/㎏), blood samples were collected at 2, 4, 6, 8, 10, 15, 20, 30, 45, 60 and 120 minutes. Urine samples were collected at 1-hr interval for 4 hr. Platinum concentrations in plasma and urine were measured using an inductively coupled plasmamass spectrometer. The plasma concentration-time curves were biphasic for all drugs during the time period studied. Compared with cisplatin, KBP31705-C127 showed similar decay patterns in the alpha- and beta-phases with slightly lower plasma concentrations. Urinary platinum excretion for cisplatin and KBP31705-C 127 was 56 and 52% of the administered dose in 4 hr, respectively. With regard to carboplatin and KBP30603-901, a similar decay pattern was also observed in the alpha-phase. The half life of KBP30603-901 in the beta-phase, however, was much longer than that of carboplatin, which was consistent with the urinary excretion results that 46 and 59% of the administered dose were excreted in the urine in 4hr, respectively. The results suggest that platinum coordination complexes are primarily excreted via the renal route and KBP30603-901 can elicit longer duration of action due to slower renal excretion compared to carboplatin.