• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.349-353
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• 1996

The present study examined pharmacokinetic profiles of KBP31705-Cl27 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 mg/kg), KBP31705-C127 (2 mg/kg), carboplatin (20 mg/kg) or KBP30603-901 (20 mg/kg), 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 patters in the alpha- and betaphases 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 KBP 30603-901, 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.243-243
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• 1996

백금착물 항암제 후보물질로서 합성된 KBP31705-Cl27, KBP30603-901을 기존 화합물인 cisplatin 및 carboplatin과 pharmacokinetic profile을 비교 검토하였다. 웅성 Sprague-Dawley rat을 sodium pentobarbital 마취하에서 방광 및 대퇴동맥과 정맥에 polyethylene tubing을 사용하여 catheterization시켰다. Urine 배출이 안정화되었을 때 대퇴정맥내로 cisplatin과 KBP31705-Cl27은 2 mg/kg, carboplatin과 KBP 30603-901은 20mg/kg 용량으로 주사한 후 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120 분에 대퇴동맥으로부터 혈액을 채취하였으며 urine은 약물투여 후 1시간 간격으로 4시간동안 채취하였다. Plasma와 urine중의 platinum농도는 inductively coupled plasma-mass spectrometer를 사용하여 측정하였고, pharmacokinetic parameters는 non-linear least square computer Program인 PCNONLIN을 이용하여 산출되었다. 혈중 platinum농도와 시간의 관계에서 KBP31705-Cl27은 cisplatin과 비교하여 alpha-phase에서 혈중 농도는 낮지만 비슷한 양상을 나타내었고, beta-phase에서는 비교적 느리게 소실됨을 보였다. Urine으로 4시간동안 배출된 platinum양은 각각 투여량의 52, 56%로서 두 약물에서 비슷하였다. 또한 KBP30603-901은 carboplatin과 비교하여 alpha-phase는 거의 비슷한 패턴을 나타내었으나, beta-phase는 훨씬 느리게 감소하여 반감기가 길다는 것을 보여 주었으며 또한 이것은 urine으로 4시간동안 배출된 platinum양이 KBP30603-901의 경우 투여량의 46%로서 carboplatin의 59%보다 적게 배출된다는 data와도 일관됨을 보여주었다. 이상의 결과로 볼 때 KBP30603-901이 다른 백금착물 항암제보다 체내에 머무르는 시간이 길어 혈중에서 보다 오랜 시간동안 머물러 높은 유효농도를 유지할 수 있을 것으로 사료된다.