• Proceedings of the PSK Conference
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• 2003.10b
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• pp.241.2-241.2
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• 2003

The purpose of this study was to investigate the effect of quercetin(2.0, 10, 20 mg/kg; combined or pretreated) on the pharmacokinetic parameters and the bioavailability of diltiazem(15mg/kg) orally to rabbits. The plasma concentration of diltiazem pretreated with quercetin(pretreated group) were increased significantly (p<0.01) compared to that of control, but those of diltiazem combined with quercetin(combined group) were not affected. Area under the plasma concentration-time curve (AUC) of diltiazem pretreated with quercetin was significantly ( p<0.01) higher than that of control (omitted)

• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.299-304
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• 2003

The purpose of this study was to investigate the effect of coadministration (2.5, 10, 20 mg/kg) and 3 or 7 days-pretreatment (10 mg/kg) of diltiazem on the pharmacokinetic parameters of paclitaxel (50 mg/kg) given orally in rats. The plasma concentrations of paclitaxel coadministered or pretreated with diltiazem were significantly (p<0.05 at 20 mg/kg coadmin., p<0.05 at pretreat.) increased compared to that of control, from 0.5 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel coadministered or pretreated with diltiazem was significantly (p<0.05 at 20 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control. Peak concentrations $(C_{max})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg coadmn. and pretreat.) increased compared to that of control. Elimination rate constants $(K_{el})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg and 7 days-pretreat.) reduced compared to those of control. Half-life $(t_{1/2})$ and mean residence time (MRT) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg ad 7 days-pretreat.) prolonged compared to those of control. Absolute bioavailability (AB%) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg and 3 days-pretreat, p<0.01 at 7 days -pretreat.) increased compared to that of control. Based on these results, it might be considered that diltiazem may inhibit cytochrome $P_{450}$ and P-glycoprotein, which are respectively engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

• Analytical Science and Technology
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• v.34 no.5
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• pp.193-201
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• 2021

We have demonstrated a sensitive analytical method of measuring oleracone D in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oleracone D and oleracone F (internal standard) in mouse plasma samples were processed using a liquid-liquid extraction method with methyl tertbutyl ether, resulting in high and reproducible extraction recovery (80.19-82.49 %). No interfering peaks around the peak elution time of oleracone D and oleracone F were observed. The standard calibration curves for oleracone D ranged from 0.5 to 100 ng/mL and were linear with r² of 0.992. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. The pharmacokinetics of oleracone D following intravenous and oral administration of oleracone D at doses of 5 mg/kg and 30 mg/kg, respectively, were investigated. When oleracone D was intravenously injected, it had first-order elimination kinetics with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 0.95 %, with multi-exponential kinetics. The low aqueous solubility and a high oral dose of oleracone D may explain the different elimination kinetics of oleracone D between intravenous and oral administration. Collectively, this newly developed sensitive LC-MS/MS method of oleracone D could be successfully utilized for investigating the pharmacokinetic properties of this compound and could be used in future studies for the lead optimization and biopharmaceutic investigation of oleracone D.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.265-269
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• 2002

The purpose of this study was to report the pharmacokinetic changes of cyclosporine after oral administration of cyclosporine, 10 mg/kg, in rabbits coadministered or pretreated twice per day for 3 days with nimodipine, dose of 5 mg/kg. The area under the plasma concentration-time curve (AUC) of cyclosporine was significantly higher in rabbits pretreated with nimodipine than that in control rabbits (p＜0.01), showing about 149％ increased relative bioavailability. The peak plasma concentration (C$_{max}$), elimination half-life (t$_{1}$2/) and MRT of cyclosporine were increased significantly (p＜0.05) in rabbits pretreated with nimodipine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant and total body clearance by pretreated with nimodipine. The effects of nimodipine on the pharmacokinetics of oral cyclosporine were more considerable in rabbits pretreated with nimodipine compared with those in control rabbits. The results suggest that the dosage of cyclosporine should be adjusted when the drug would be coadministered chronically with nimodipine in a clinical situation.n.

• YAKHAK HOEJI
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• v.32 no.5
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• pp.319-327
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• 1988

Pharmacokinetic interaction of cimetidine and isoniazid was investigated in the rabbits. Isoniazid was administered orally at a dose of 30mg/kg to six rabbits after 10, 20, and 30mg/kg pretreatment of cimetidine twice a day for 10days. Concentration of the free and the total isoniazid in the blood and the urine was determined by spectrophotometer. Relative bioavailability and biological half-life($t\frac{1}{2}{\beta}$) were increased significantly by cimetidine pretreatment. Overall elimination rate constant and total clearance of isoniazid were decreased significantly by cimetidine pretreatment. The ratio of metabolites to isoniazid in the blood and the urine was decreased significantly by cimetidine pretreatment. Relative bioavailability, INAH to metabolites ratio in the blood and decrease in total clearance were highly correlated with the does of cimetidine pretreated. This result might be due to the inhibition of isoniazid metabolism in the liver by cimetidine pretreatment.

• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.15-21
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• 2004

The pharmacokinetics of orally administered verapamil (10 mg/kg) was studied in six rabbits after 20 min pretreatment with quercetin ad coadministration of quercetin (2.0 mg/kg, 1 mg/g and 20 mg/kg, respectively). Pretreatment with quercetin significantly (p < 0.01, p < 0.05) increased the plasma concentration of verapamil. However, coadministration of quercetin showed no significantly effect on the pharmacokinetic parameters of verapamil. The elimination rate constant $(K_{el})$ of verapamil pretreated with quercetin (1 mg/kg and 20 mg/kg) was significantly (p < 0.05) reduced compared with control. The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of verapamil pretreated with quercetin (2.0 mg/kg, 10 mg/kg and 20 mg/kg) were increased significantly (p < 0.01, p < 0.05) compared with control. Pretreatment with quercetin (2.0 mg/kg, 10 mg/kg and 20 mg/kg) significantly (p < 0.01, p < 0.05) increased the relative bioavailability of verapamil to 159 - 219%. These results suggest that quercetin alters disposition of verapamil by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of verapamil should be adjusted when it is administered chronically with quercetin in a clinical situation.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.200-204
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• 2010

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg) with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life ($t_{1/2}$) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance ($CL_t$). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.

• Korean Journal of Clinical Pharmacy
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• v.17 no.1
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• pp.33-37
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• 2007

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of diltiazem (15 mg/kg) after oral administration of diltiazem with or without atorvastatin (0.5, 1.5 and 3.0 mg/kg) in rats. Coadministration of atorvastatin increased significantly (p<0.05, 3.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of diltiazem compared to the control group. The total plasma clearance (CL/F) of diltiazem was decreased significantly (p<0.05, 3.0 mg/kg) compared to the control group. The relative bioavailability (RB%) of diltiazem was increased from 1.14- to 1.49-fold. Coadministration of atorvastatin did not significantly change the elimination rate constant $(K_{el})$, terminal half-life $(T_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of diltiazem. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.243-247
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• 2011

Rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, has been shown to be anti-inflammatory. In the present study, a possible interaction between rutaecarpine and caffeine was investigated in male Sprague Dawley rats. Twenty four hr after the oral pretreatment with rutaecarpine at 80 mg/kg for three consecutive days, rats were treated intravenously with 10 mg/kg of caffeine. Compared with control rats, the pharmacokinetic parameters of caffeine in rutaecarpine-pretreated rats were significantly changed, possibly due to the rapid metabolism. The production of three metabolites of caffeine (i.e., paraxanthine, theobromine and theophylline) was also significantly changed in rats pretreated with rutaecarpine. The present results suggest that oral rutaecarpine would change the intravenous pharmacokinetic characteristics of caffeine.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.57-62
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• 2006

The purpose of this study was to investigate the effect of naringenin, one of flavonoids, on the pharmacokinetics and bioavailability of diltiazem (15 mg/kg) after oral administration of diltiazem with or without naringenin (2.0, 10 and 20 mg/kg) in rabbits. Coadministration of naringenin increased the absorption rate constant $(K_a)$, the area under the plasma concentration-time curve (AUC) and peak concentration $(C_{max})$ of diltiazem compared to the control group, but only significantly (p<0.05) by 10mg/kg of naringenin coadministration. The absolute bioavailability (AB%) of diltiazem by coadministration ranges from 7.8% to 10.3%, increased more than control (7.2%), and relative bioavailability (RB%) of diltiazem is increased from 1.08- to 1.43-fold. Coadministration caused on significant changes in the terminal half-lives $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of diltiazem. On the other hand, coadministration of naringenin increased the AUC desacetyldiltiazem, significantly at the dose of 10mg/kg. But the metabolite ratio (MR) was decreased, significantly at 10mg/kg of naringenin. Based on these results, we can make a conclusion that the increased bioavailability and the significant changes of these pharmacokinetic parameters might be due to naringenin, which possess the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein efflux pump in the intestinal mucosa.