• Analytical Science and Technology
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• v.34 no.2
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• pp.37-45
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• 2021

A rapid and simple LC-MS/MS analytical method in determining Jaspine B has been developed and validated in rat plasma. The standard curve value was 25 - 5000 ng/mL and the linearity, inter-day and intra-day accuracy and precision were within 15.0 % of relative standard deviation (RSD). The mean recoveries of Jaspine B ranged from 87.5 % to 91.2 % with less than 3.70 % RSD and the matrix effects ranged from 91.1 % to 108.2 % with less than 2.6 % RSD. The validated LC-MS/MS analytical method of Jaspine B was successfully applied to investigate the dose-escalated pharmacokinetic study of Jaspine B in rats following an intravenous injection of Jaspine B at a dose range of 1 - 10 mg/kg. The initial plasma concentrations and area under plasma concentration curves showed a good correlation with intravenous Jaspine B dose, indicating the dose independent pharmacokinetics of Jaspine B in rats. In conclusion, this analytical method for Jaspine B can be easily applied in the bioanalysis and pharmacokinetic studies of Jaspine B, including its administration at multiple therapeutic doses, or for making pharmacokinetic comparisons for the oral formulations of Jaspine B in small experimental animals as well as in vivo pharmacokinetic-pharmacodynamic correlation studies.

• Mass Spectrometry Letters
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• v.12 no.1
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• pp.16-20
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• 2021

We aimed to compare the content of ginsenosides and the pharmacokinetics after the oral administration of four different ginseng products at a dose of 1 g/kg in rats. The four different ginseng products were fresh ginseng extract, red ginseng extract, white ginseng extract, and saponin enriched white ginseng extract prepared from the radix of Panax ginseng C.A. Meyer. The ginsenoside concentrations in the ginseng product and the rat plasma samples were determined using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eight or nine ginsenosides of the 15 tested ginsenosides were detected; however, the content and total ginsenosides varied depending on the preparation method. Moreover, the content of triglycosylated ginsenosides was higher than that of diglycosylated ginsenosides, and deglycosylated ginsenosides were not present in any preparation. After the single oral administrations of four different ginseng products in rats, only four ginsenosides, such as 20(S)-ginsenosides Rb1 (GRb1), GRb2, GRc, and GRd, were detected in the rat plasma samples among the 15 ginsenosides tested. The plasma concentrations of GRb1, GRb2, GRc, and GRd were different depends on the preparation method but pharmacokinetic features of the four ginseng products were similar. In conclusion, a good correlation between the area under the concentration curve and the content of GRb1, GRb2, and GRc, but not GRd, in the ginseng products was identified and it might be the result of their higher content and intestinal biotransformation of the ginseng product.

• Journal of Society of Preventive Korean Medicine
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• v.17 no.2
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• pp.139-155
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• 2013

Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.446-452
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• 2016

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.47-53
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• 1999

Gastrodia elata (GE) is an oriental medicinal herb which has been used traditionally for the treatment of various brain diseases including convulsion and epilepsy. The purpose of this study was to determine pharmacokinetic parameters of 4-hydroxy-3-methoxybenzaldehyde (HMBA) and p-hydroxybenzaldehyde (PHBA), constituents of GE, in rats. Male rats were cannulated in the femoral vein, femoral artery, bile duct and ureter. They received a single i.v. bolus dose of either HMBA or PHBA through the femoral vein. The concentration of HMBA or PHBA in plasma, bile and urine samples were analyzed by reversed-phase HPLC. HMBA and PHBA have very short half-lives, i.e. 4.03 and 2.26 minutes respectively. Most of HMBA and PHBA were thought to be eliminated through metabolism as the metabolized fraction approaches unity. Derivatives of HMBA or PHBA with longer biological half-lives should be designed to develop better anticonvulsants and more complete qualitative and quantitative understanding of the overall pharmacokinetic fate of these compounds awaits further investigation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.97-97
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• 1995

On the combination of antacid, the pharmacokinetics and gastric adhesion of $\^$14/C-aceglutamide aluminum complex($\^$14/C-AGA) were examined in rats. Specially, This study was focused on the drug interaction that the coadministration of antacid may affect the oral absorption and gastric adhesion of aceglutamide aluminum complex(AGA). After the oral administration of $\^$14/C-AGA and antacid to rats, the radioactivity of plasma and urinary recovery was lower than that of $\^$14/C-AGA administered group. Relatively, the cumulative recovery of radioactivity in feces was increased significantly. The comparative bioavailability of $\^$14/C-AGA from the plasma concentration-time curve and urinary recovery was about 60%. in vitro, the effect of antacid in the gastric adhesion of AGA was not significantly different between AGA and AGA/antacid treatment. And it accorded well with the result of in vivo experiment. In conclusion, on the combination of antacid, the oral absorption of AGA was decreased but the gastric adhesion was not affected in respect of drug interaction.

• Journal of Pharmaceutical Investigation
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• v.11 no.4
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• pp.1-11
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• 1981

In order to elucidate the effects of Panax Ginseng on the pharmacokinetics of sulfobromophthalein (BSP) in a pathological condition, patho-physiological changes, the kinetics of the disappearance of BSP from the blood and appearance in the bile were studied in rats. Group I , the control group, was produced by repeated injection of olive oil 0.1ml/100g under the skin of the back twice a week for 9 weeks. Group II , the Ginseng pretreated group, was produced by administration of Ginseng total saponin 200mg/kg/day P.O. for 10 days and subsequent injection of $CCl_4$ 0.1ml/100g under the skin of the back twice a week for 9 weeks. Group III , the chronically intoxicated group, was produced by repeated injection of $CCl_4$ 0.1ml/100g under the skin of the back twice a week for 9 weeks. The results obtained were summarized as follows; 1. The activities of GOT GPT of rat blood serum, body weight, and liver weight were affected by the pretreatment with Ginseng saponin. 2. The kinetics of the disappearance of BSP from the blood were affected by the pretreatment with Ginseng saponin. 3. The appearance of BSP in the bile was significantly affected by the pretreatment with Ginseng saponin.

• Archives of Pharmacal Research
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• v.8 no.3
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• pp.177-186
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• 1985

Effect of food on the absorption characteristics of oral rifampicin was studied in the fasted rats. Rifampicin dissolved in a new cosolvent was also injected to the rats intravenously, and the pharmacokinetic analysis was performed to explain the effect of food on the gastrointestinal absorption of rifampicin. Rifampicin was absorbed rapidly and completely in the fasting state. Food had a profound effect on the gastrointestinal absorption of rifampicin, i. e., bioavailability and the extent of absorption were decreased to less than one-third of the fasting state in the postprandial state. Food seemed to imhibit the absorption and reabsorption of rifampicin in the gastrointestinal tract, but not the absorption rate constant. Hepatobiliary excretion seemed to be the major route of elimination, since the renal clearance accounted for only 8 % of the systemic clearance. Nevertheless, first-pass effect was negligibly small and most of rifampicin absorbed could reach systemic circulation. Serum concentration change of oral rifampicin on multiple dosing differed markedly in the fasting and postprandial state, which suggested the need of careful adjustment of dosage regimen in both states.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.763-767
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• 2003

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm $\times$ 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mm$\times$4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time ($T_{1/2(\alpha)}$) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time ($T_{1/2(\beta)}$) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.601-610
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• 2024

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CL_NR) and renal clearance (CL_R) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CL_NR, and CL_R) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance. Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.