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

• 한국임상약학회지
• /
• 제9권2호
• /
• 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.

• 한국임상약학회지
• /
• 제11권2호
• /
• pp.57-61
• /
• 2001

The effect of circadian rhythm on the pharmacokinetics of acebutolol was studied in rabbits administered intravenous 5 mg/kg dose of acebutolol at 09:00 in the morning (a.m) and 22:00 in the evening (p.m). A significant effect of circadian rhythm of pbarmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance (CLt), higher plasma concentration and the area under the plasma concentration time curve (AUC) when acebutolol was given in the evening. The plasma concentration of acebutolol was increased significantly (p<0.05) at 12-24 hr after dosing in the evening. The AUC was greater in the evening $(111\%)$ than that in the morning and $CL_t$, was higher when acebutolol was given in the morning ($1.12\pm0.24$ ml/hr) versus in the evening ($1.01\pm0.22$ ml/hr), but those were not significant. Therefore, It is reasonable to consider individual circadian rhythm for effective dosage regimen of acebutolol in clinical chronotherapeutics.

• Journal of Pharmaceutical Investigation
• /
• 제24권4호
• /
• pp.289-295
• /
• 1994

Pharmacokinetic drug interaction between phenytoin and verapamil was investigated following i.v. administration of two drugs concomitantly to rabbits. Verapamil was coadministered with phenytoin (5 mg/kg) to rabbits at the doses of 0.5,1 and 2 mg/kg, respectively. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 1mg and 2mg/kg of verapamil, respectively. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin should be administered with verapamil in clinical practice.

• Journal of Pharmaceutical Investigation
• /
• 제26권2호
• /
• pp.113-117
• /
• 1996

This study was attempted to investigate the pharmacokinetic interaction between sodium valproate (4, 8, 16 mg/kg, i.v.) and phenytoin (4 mg/kg, i.v.) in rabbits. The plasma concentration and area under the curve (AUC) of phenytoin were increased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (4, 8, 16 mg/kg) in rabbits. The volume or distribution and total body clearance of phenytoin were decreased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (8, 16 mg/kg) in rabbit. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin will be coadministered with sodium valproate in clinical use.

• Journal of Pharmaceutical Investigation
• /
• 제19권1호
• /
• pp.15-20
• /
• 1989

The displacement of protein bound sulfonamides (sulfisoxazole, sulfamethoxazole, sulfisomidine) by furosemide was investigated in bovine serum albumin by equilibrium dialysis method. Furosemide $(2{\times}10^{-4}M)$ in bovine serum albumin ($7.24{\times}10^{-5}$, $1.45{\times}10^{-4}$, $2.89{\times}10^{-4}M$). Sulfisoxa캐1e and furosemide were bound reversibly to bovine serum albumin and competitive for the same binding sites when administered together. Consequently, dosage regimen of sulfisoxazole should be adjusted carefully when sulfisoxazole is administered along with furosemide.

• 약학회지
• /
• 제35권5호
• /
• pp.379-383
• /
• 1991

This study was attempted to investgate the pharmacokinetics of theophylline (4 mg/kg i.v) in the rabbits pretreated with propranolol (1 and 2.5 mg/kg/hr, infusion) for four hours. The plasma concentration and AUC of theophylline were increased in rabbits pretreated with propranolol as compared with those of normal rabbits. The amount of cumulative urinary excretion and renal clearance and total body clearance were decreased in rabbits pretreated with propranolol as compared with those of normal rabbits. The apparent volume of distribution was slightly affected by change of the clearance of theophylline. From the results of this experiment, it is desirable that dosage regimen of theophylline should be adjusted when theophylline combined with propranolol in clinical pharmacy practice.

• Journal of Pharmaceutical Investigation
• /
• 제23권1호
• /
• pp.27-32
• /
• 1993

Pharmacokinetic drug interaction between phenytoin and diltiazem was investigated following i.v. administration concomitantly to rabbits. Diltiazem was coadministered at doses of 1, 2 and 3 mg/kg, respectively, with phenytoin (5 mg/kg) to rabbits. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 2 mg and 3 mg/kg of diltiazem. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin should be administered with diltiazem in clinical practice.

• 한국임상약학회지
• /
• 제9권1호
• /
• pp.66-70
• /
• 1999

The effect of circadian rhythm on cyclosporine pharmacokinetics was studied in rabbits after oral administration of 10 mg/kg dose of cyclosporine at 10:00 a.m. and 10:00 p.m. The blood concentration data were subjected to simultaneous computer nonlinear least squares regression analysis using a 1-compartment pharmacokinetic model. The blood concentrations of cyclosporine at 10:00 a. m. were increased significantly during 2-6 hr compared to those at 10:00 p.m. The area under the blood concentration-time curve (AUC) and peak concentration $(C_{max})$ of cyclosporine at 10:00 a.m. were increased significantly compared to those at 10:00 p.m. The mean total body clearance (CL) of cyclosporine at 10:00 a.m. were decreased significantly compared to those at 10:00 p.m. It is reasonable to consider individual circadian rhythm for effective dosage regimen of cyclosporine in therapeutics.

• 약학회지
• /
• 제36권4호
• /
• pp.321-325
• /
• 1992

Pharmacokinetic interaction of theophylline with pefloxacin following i.v. administrations was investigated in rabbits. Pefloxacin was coadministrated at doses of 10 and 20 mg/kg or previously administered for 6 days 10 and 20 mg/kg. Plasma concentration and AUC of theophylline were increased significantly (p<0.05) and the renal clearance $(CL_r)$, total body clearance $(CL_r)$ and the volume of distribution $(Vd_{ss})$ were decreased significantly (p<0.005) by the pretreatment. It demonstrates that adjustment of dosage regimen of theophylline should be considered when concomitant administration of pefloxacin is prescribed.