• Korean Journal of Clinical Pharmacy
• /
• v.12 no.2
• /
• pp.91-95
• /
• 2002

The pharmacokinetics of intravenous paclitaxel (1 mg/kg) were investigated in rabbits with renal failure induced by folic acid. The area under the plasma concentration-time curve from time zero to time infinity (AUC) of paclitaxel was significantly (p<0.05) greater in rabbits with severe renal failure induced by folic acid $(1030\pm382)$ compared to that in rabbits with in moderate renal failure induced by folic acid $(780\pm209\;ng/ml{\cdot}hr)$. The apparent volume of distribution (Vd) $(0.008\pm0.002\;L/kg)$ and the elimination rate constant $(\beta)\;(0.09\pm0.025\;hr^{-1})$ of paclitaxel in rabbits with severe renal failure were significantly (p<0.05) smaller and slower respectively than those of control rabbits $(0.016\pm0.004\;L/kg,\;0.12\pm0.03\;hr^{-1})$, but not significantly different compared with that in rabbits with moderate renal failure $(0.010\pm0.003\;L/kg,\;0.10\pm0.026\;hr^{-1})$. total body clearance (CL) of paclitaxel in rabbits with severe renal failure $(0.97\pm0.183\;L/hr/kg)$ was significantly (p<0.05) slower than that in control rabbits $(1.68\pm0.440\;L/hr/kg)$, but not significantly different compared with that in rabbits with in moderate renal failure $(1.28\pm0.311\;L/hr/kg)$. The terminal half-life ($t_{1/2}$) of paclitaxel in rabbits with severe renal failure $(7.46\pm2.16\;hr)$ was significantly (p<0.05) longer than that in control rabbits $(5.75\pm1.44\;hr)$, but not significantly different compared to that in rabbits with moderate renal failure rabbits $(6.67\pm1.76\;hr)$. The above data could be at least partly decrease in due to paclitaxel excretion in rabbits with renal failure, since $7-15\%$ of interavenous paclitaxel was excreted via kidney as unchanged forms plus its metablites.

• Korean Journal of Clinical Pharmacy
• /
• v.9 no.2
• /
• pp.92-96
• /
• 1999

The pharmacokinetics of carbamazepine(100 mg/kg, oral) in the folic acid-induced renal failure rabbits was studied. Renal failure was induced by the i.v. injection of folic acid (50, 100, and 200 mg/kg). At folic acid dose of 100 and 200 mg/kg, the serum creatinine concentration (Scr) and blood urea nitrogen (BUN) increased significantly compared with control rabbits. Plasma concentrations and area under the plasma level-time curve (AUC) of carbamazepine increased significantly at folic acid dose of 100 and 200 mg/kg. The elimination rate constant (Kel) of carbamazepine decreased significantly, and half-life $(t_{1/2})$ of carbamazepine increased significantly at folic acid dose of 100 and 200 mg/kg. The serum creatinine concentration (Scr) correlated well with AUC and elimination rate constant (Kel) of carbamazepine, as well as BUN with AUC and elimination rate constant (Kel) of carbamazepine. These results suggest that adjustment of the dosage regimen of carbamazepine is desirable, and serum creatinine concentration (Scr) as well as BUN can be used for adjusting the dosage regimen of carbamazepine in renal failure.