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RISS 인기검색어
- 검색키워드
- 저자 : Jun-ShikChoi (검색결과 2 건)
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Pharmacokinetics of Paclitaxel in Rabbits with Carbon Tetrachloride-Induced Hepatic Failure
Jun-ShikChoi 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.6
The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits with carbon tetrachloride- induced hepatic failure. The area under the plasma concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased in severe carbon tetrachloride-induced hepatic failure rabbits (1364.54 ± 382.07 ng/ml . hr) compared to that of normal rabbits (567.52 ± 141.88 ng/ml . hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits (803.1 ± 208.81 ng/ml . hr). The volume of distribution (Vd) (6.25 ± 1.56 L) and the elimination rate constant(b) (0.09 ± 0.025 hr-1) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were significantly (p<0.05) decreased compared to those of normal rabbits (11.65 ± 2.91 L, 0.12 ± 0.030 hr-1), but not significantly in moderate carbon tetrachlorideinduced hepatic failure rabbits (9.46 ± 2.37 L, 0.10 ± 0.026 hr-1). Total body clearance (CLt) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits (0.733 ± 0.183 L/hr/kg) was significantly (p<0.01) decreased compared to that of normal rabbits (1.762 ± 0.440 L/hr/kg), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits (1.245 ± 0.311 L/hr/kg). The half-life(t1/2) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits (7.71 ± 2.16 hr) was significantly (p<0.05) increased compared to that of normal rabbits (5.75 ± 1.44 hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits (6.77 ± 1.76 hr). This results could be due to inhibition of paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially metabolized in liver. The findings suggest that the dosage regimen of paclitaxel should be adjusted when the drug would be administered in patients with liver disorder in a clinical situation.
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