• Archives of Pharmacal Research
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• 제26권11호
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• pp.979-983
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• 2003

The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure. The plasma concentrations of tolbutamide were significantly elevated (p<0.05) during 9 to 24 h in rabbits with mild or medium folate-induced renal failure. Consequently, the area under the plasma concentration-time curves (AUC) was significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal failure rabbits (i.e., 2906 $\mu$g/mL$.$h for mild renal failure and 4074 $\mu$g/mL$.$h for moderate renal failure) than that in normal rabbits (i.e., 2295 $\mu$g/mL$.$h). The cumulative urinary excretion of tolbutamide was significantly depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg) compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly decreased in medium renal failure rabbits (i.e., 0.027 $h^{-1}$) than that in normal rabbits (i.e., 0.044 $h^{-1}$ ); As a result, the terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is consistent with the hypothesis that the alteration is mediated by the depressed metabolic elimination of the drug by the induction of renal failure. Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.333-337
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• 2001

The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg was given to the rabbits either orally (n=6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration ($C_{max}$) of DTZ were significantly increased in mild and medium folate-induced renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly decreased in mild and medium folate-induced renal failure rabbits. The volume of distribution ($V_{d}$) and total body clearance ($CL_{t}$) of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimination rate constant ($\beta$) of DTZ was significantly decreased in folate-induced renal failure rabbits, but that of DAD was significantly increased. These findings suggest that the hepatic metabolism of DTZ was inhibited and the $V_{d}$, $CL_{t}$ and $\beta$ of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.

• 한국임상약학회지
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• 제12권2호
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• pp.91-95
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• 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.

• Journal of Pharmaceutical Investigation
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• 제25권3호
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• pp.265-270
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• 1995

The pharmacokinetics of norfloxacin (100 mg/kg, oral) in renal failure rabbits was studied. Renal failure rabbits were induced by the i.v. injection of folate (50,100 and 150 mg/kg). These produced significant increases of serum creatinine concentration $(S_{cr})$ and blood urea nitrogen (BUN). Plasma concentration and AUC of norfloxacin significantly increased. Elimination rate constant $(K_{el})$ of norfloxacin significantly decreased, and half-life $(t_{1/2})$ of norfloxacin significantly increased. Correlation between serum creatinine concentration $(S_{cr})$ and half-life $(t_{1/2})$ of norfloxacin, and correlation between BUN and AUC of norfloxacin have linear relationship respectively. These results suggest that adjustment or the dosage regimen of norfloxacin is desirable, and serum creatinine concentration $(S_{cr})$ as well as BUN can be used an index for adjusting the dosage regimen of norfloxacin in renal failure.

• 생약학회지
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• 제15권4호
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• pp.179-187
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• 1984

To investigate the recorded efficacy in Oriental medical references and effects in clinics, experimental studies were undertaken to estimate 'Palmiwhan' to the diuretic effect in normal rats, rabbits and rats with $HgCl_2-induced$ acute renal failure and hypotensive effects on the nephrogenous hypertension in rabbits with $HgCl_2-induced$ acute renal failure. The results of this study were summarized as follows; Increase in urinary volume, urinary $Na^+\;and\;Cl^-$ excretions were significantly recognized in normal rats and rabbits. Increase in urinary volume, urinary $Na^+\;and\;Cl^-$ excretions were significantly shown in rats with 2mg/kg $HgCl_2-induced$ acute renal failure. Although plasma electrolyte and creatinine levels were little affected, plasma urea nitrogen levels were significantly elevated in normal rats and 2mg/kg $HgCl_2-induced$ acute renal failure of rats. Although the blood pressure was not affected in normal rabbits and cats, hypotensive actions due to the diuretic effect were recognized in rabbits $HgCl_2-induced$ acute renal failure.

• Journal of Pharmaceutical Investigation
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• 제16권4호
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• pp.152-157
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• 1986

The pharmacokinetics of sulfamethoxazole were investigated in rabbits with folate-induced renal failure. The blood level, area under the blood concentration curve (AUC) and biological half-life were increased significantly, and the urinary excretion was decreased significantly compared with those of normal rabbits. Correlation of serum creatinine concentration and AUC, biological half-life, and correlation of creatinine clearance and renal clearance have linear relationship respectively. From these results, dosage regimen of sulfamethoxazole is considered to be adjusted for effective and safe therapy in renal failure.

• 약학회지
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• 제29권4호
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• pp.216-219
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• 1985

The phormacokinetics of acetaminophen were investigated in rabbits with folate-induced renal failure. The blood level, the area under the blood concentraction curve(AUC) and the biological half-life were increased significantly, and the urinary excretion was decreased significantly as compared with those of normal rabbits. Serum creatinine concentration and AUC, creatinine clearance and renal clearance have linear relationship respectively. Dosage regimen of acetaminophen was considered to be adjusted in renal failure.

• 한국임상약학회지
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• 제9권2호
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• pp.92-96
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• 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.

• Journal of Acupuncture Research
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• 제19권3호
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• pp.156-167
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• 2002

The present study was carried out to determine if Scutellaria balicalensis Georgi. extract (SBGE) exerts beneficial effect against the renal failure in rabbits. Rabbits were pretreated with SBGE orally for 7 days, followed by cisplatin injection (5 mg/kg, i.p.), cisplatin injection caused an increase in serum creatinine level, which was accompanied by a reduction in GFR. The fractional excretion of Na+, K+, glucose, and phosphate increased in cisplatin-treated animals, which was prevented by SBGE pretreatment. The uptake of p-aminohippurate, an organic anion, in renal cortical slices was inhibited by the administration of cisplatin, and the effect was prevented by SBGE. cisplatin injection increased lipid peroxidation, which was prevented by SBGE pretreatment. These results indicate that lipid peroxidation plays a critical role in cisplatin-induced acute renal failure. SBGE exerts the protective effect against acute renal failure induced by cisplatin, and its effect may be attributed to an antioxidant action.

• 약학회지
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• 제34권6호
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• pp.401-406
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• 1990

The Pharmacokinetics of furosemide (5 mg/kg iv) was investigated in rabbits with folate (75 mg/kg, 150 mg/kg 300 mg/ug, iv) induced renal failure. The plasma concentration was increased and urinary excretion was decreased significantly compared with those of normal rabbits. ${\alpha},\;{\beta}\;and\;K_{12},\;K_{21},\;K_{10}$ were decreased, $t_{1/2}$ and AUC were increased significantly. Correlation of serum creatinine concentration and AUC, renal clearance have linear relationship respectively. In short, dosage regimen of furosemide is considered to be adjusted in the dose size and the dosing interval by degree of serum creatinine concentration.