• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.206-212
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• 2013

Purpose: The aim of this study was to investigate the effect of nimodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Methods: Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of nimodipine (0.5 or 2 mg/kg) in rats. The effect of nimodipine on the P-glycoprotein as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Results: Nimodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $10.2{\mu}M$. Compared to those animals in the oral control group (warfarin without nimodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.5 mg/kg, P<0.05; 2 mg/kg, P<0.01) by 31.3-57.6%, and the peak plasma concentration ($C_{max}$) was significantly higher (2 mg/kg, P<0.05) by 29.4% after oral administration of warfarin with nimodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.31- to 1.58-fold and the absolute bioavailability of warfarin with nimodipine was significantly greater by 64.1-76.9% compared to that in the control group (48.7%). In contrast, nimodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Conclusion: Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism rather than P-glycoprotein-mediated efflux by nimodipine.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.493-497
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• 2011

The aim of this study was to investigate the effect of amlodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of amlodipine (0.1 or 0.4 mg/kg) in rats. The effect of amlodipine on the P-glycoprotein (P-gp) as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Amlodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 9.1 ${\mu}M$. Compared to those animals in the oral control group (warfarin without amlodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.1 mg/kg, p<0.05; 0.4 mg/kg, p<0.01) by 26.5-53.5%, and the peak plasma concentration ($C_{max}$) was significantly higher (0.4 mg/kg, p<0.05) by 26.2% after oral administration of warfarin with amlodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.26- to 1.53-fold and the absolute bioavailability of warfarin with amlodipine was significantly greater by 61.7-72.5% compared to that in the control group (47.4%). In contrast, amlodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver rather than renal elimination and P-gp by amlodipine.

• Journal of Korean Medicine for Obesity Research
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• v.17 no.2
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• pp.111-118
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• 2017

Objectives: This study was conducted to evaluate the effects of Pueraria lobata (PL) extract on obesity related hormones in rats with estrogen deficiency. Methods: The experiments were performed with the use of ovariectomized rats as estrogen-deficient obesity rat model. They were grouped Normal (sham operation group), Control (ovariectomy group), 50 mg/kg PL (ovariectomy group＋50 mg/kg of PL), 100 mg/kg PL (ovariectomy group＋100 mg/kg of PL), 200 mg/kg PL (ovariectomy group＋200 mg/kg of PL). PL extract was orally administered for 8 weeks once a day. Body weights and serum levels of hormones, such as leptin, estradiol, cholecystokinin (CCK), ghrelin, and adiponectin were estimated by ELISA. Results: PL extract significantly decreased body weight, the serum levels of leptin in estrogen-deficient obesity rats. PL extract significantly increased the serum levels of estradiol and CCK. However, PL extract did not directly effect on the levels of ghrelin and adiponectin in estrogen-deficient obesity rats. Conclusions: It is concluded that PL extract reduced body weight, and regulate the hormones related to energy metabolism. PL extract decreased the serum levels of leptin. PL extract increased the serum levels of estradiol and CCK. These results indicate that PL might have potentials for treatment of obesity and complications during the menopause caused by estrogen-deficiency.

• Nutrition Research and Practice
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• v.12 no.6
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• pp.535-540
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• 2018

BACKGROUND/OBJECTIVES: Propolis has a rich source of bioactive compounds and has renal and hepatic protective properties. The purpose of this study was to investigate the beneficial effect of hydro-ethanolic extract of propolis against paracetamol-induced liver damage and impairment of kidney function, as well as hematological changes in rats. MATERIALS/METHODS: Six groups of rats were used; the first group was served as a control; the second and third groups were treated by propolis extract at a dose of 50 and 100 mg/kg.B.WT. respectively; the fourth group was treated by paracetamol (200 mg/kg.B.WT.); the fifth group was treated by propolis (50 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days; and the sixth group was treated with propolis (100 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days. All the animals were treated for a period of 15 days. At the end of the experimental period, blood samples were collected for measurement of the liver enzymes, serum albumin, protein and creatinine, blood urea nitrogen, hematological parameters, and urine volume, protein and albumin. RESULTS: Paracetamol over dose significantly lowered hemoglobin, serum total protein, albumin, and uric acid, while it significantly increased blood creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, white blood cells, and platelet count as compared to the control. However, these alterations were significantly attenuated by the use of propolis extract and the effect was dose dependent. Interestingly, propolis prevented paracetamol induced proteinuria, low hemoglobin and body weight loss. CONCLUSIONS: Propolis significantly prevented paracetamol induced renal, hepatic and hematological toxicity and might be useful in the management of liver and renal diseases particularly proteinuria.

• Toxicological Research
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• v.20 no.3
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• pp.281-292
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• 2004

The purpose of this study was to assess the single and 5 week oral dose toxicity of calcitriol and alendronate combination (1 : 10,000) treatment for osteoporosis or Paget's disease in male and female rats. In single dose oral toxicity study, the values of $LD_{50}$ of calcitriol and alendronate mixture were 750.075 mg/kg in male rats and 775.0775 mg/kg in female rats, respectively. Body weight and food consumption were continuously increased after adminstration of calcitriol and alendronate mixtures, and there was no significant changes in body weight and food consumption in all groups. In five-week oral toxicity study of calcitriol and alendronate mixture at a dose of 0.2 $\mu\textrm{g}$ + 2 mg, 1 $\mu\textrm{g}$ + 10 mg, 5 $\mu\textrm{g}$ + 50 mg and 25 $\mu\textrm{g}$ + 250 mg, respectively, there was no mortality, abnormal behavior and appearance in all groups throughout the administration period (5 weeks) and recovery period (2 weeks). Dose-dependent changes in parameters of urinalysis and hematological analysis were not observed in male and female rats treated with calcitriol and alendronate mixtures. All the values of the parameters appeared to be in the normal range. These data indicate that both calcitriol and alendronate are drugs having low toxicity in rats. NOAEL of calcitriol and alendronate mixtures were 50.005 mg/kg in 5-week oral toxicity.

• Journal of Ginseng Research
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• v.1 no.1
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• pp.33-50
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• 1976

As a continuation of series of works on the pharmacological actions of Panax ginseng. three kinds of behavioral experiments were carried out using rats and mice. The occurrence of component Posterns of general behavioral activity in rat was examined by visual scanning using the ting sample method in the ad lib. And he hunger deprivated situation. In normal ad lib. situation, the eating behavior of rat treated with 100mg/kg of ginseng saponin was significantly more frequent than that of saline control at the night and throughout the 24 hr period. But grooming was less frequent than the control at the same period. In the hunger situation followed by 90~120 hrs of feed deprivation, the locomotive activity and rearing awe significantly more often and sleeping was less frequent in the two dosage g roups of ginseng saponin (10 and 100 mg/kg) than in the saline group though out the observation period. Training of avoidance conditioning in rats was done in a two-way shuttle box. The number of conditioned response (CR) in which the animal avoided sucessfully an electric shock by running in to the other compartment of the hex was regarded as an index of learning performance. Ginseng saponin in doses of 2.5 mg/kg Produced a significantly increased CR in total avoidance tria1s compared with the control. Although other dosage groups of ginseng saponin (5.0, 50mg and 100 mg/kg) showed no significant statistical difference from the normal control, it tended to increase in CR in the ginseng groups than in the control. An aggressive behavior in mice was observed in n shock-generating fighting box. The occurrence of reflexive fighting between two animals induced by an electric shock applied to the feet war checked as an index of aggression. The occurrence of reciprocal fighting episode immediately after the onset. Of the shock was significantly decreased in the dosage group of 400 mg/kg ginseng saponin, but it did net differ in the 100 mg/kg group of ginseng saponin from the control group. The dose, 400 mg/kg of ginseng saponin, inhibited fighting behavior in more than 80% of the Pairs. but 100 mg/kg of ginseng did inhibit it in less than 20% of the pairs.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.527-533
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• 1998

6-(3,4-Dichlorophenyl)amino-7-chloro-5,8-quinolinedione (RCK50) was tested for antifungal activities in mice systemically infected with Candida albicans. The therapeutic potential of RCK50 was also assessed in comparison with ketoconazole. CK50 had $ED_{50}$ 0.22${\pm}$0.01mg/kg. Ketoconazole as a positive control had $ED_{50}$ 6.00${\pm}$1.70mg/kg. Intraperitoneally administered RCK50 at the $ED_{50}$ for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver. And administered RCK50 at the $ED_{50}$ for 14 days improved survival rates. The genotoxicities of RCK50 had been evaluated. RCK50 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. RCK50 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK50 has no genotoxic potential under these experimental conditions. Acute oral toxicity studies of RCK50 were carried out in ICR mice of both sexes. RCK50 did not show acute oral toxicities and $LD_{50}$ values were over 2,850mg/kg in ICR mice.

• Korean Journal of Food Science and Technology
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• v.40 no.3
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• pp.243-250
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• 2008

In Korean, nine tar colors are permitted in foods. This study assessed these compounds in the favorite food items of children found near elementary schools. A total of 439 items categorized under six food types were included in the analysis. The most frequently detected tar colors were tartrazine (Y4), Brilliant Blue FCF (Y5), Allura Red, and Sunset Yellow FCF, respectively. One or a mixture of two tar colors were commonly found in products such as gums, ice bars, soft drinks, and cereals. However, most often, combinations of two or three tar colors were detected. The levels of tar colors in candies, chocolates, gums, ice bars, cereals, and soft drinks were 0.11-1169.58 mg/kg, 0.73-468.02 mg/kg, 0.10-602.46 mg/kg, 0.25-162.32 mg/kg, 0.11-753.68 mg/kg, and 0.21-69.45 mg/kg, respectively. Tar color levels were higher in chocolates and gums than in soft drinks and ice bars. And Y4 and Y5 were detected at the highest levels. For ages 7-12, the total estimated daily intake (${\sum}EDI$) of each tar color ranged from 0.004 to 1.017 mg/day/person. These values were 0.02-5.98% of the FAO/WHO's acceptable daily intake (ADI).

• Toxicological Research
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• v.14 no.2
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• pp.261-271
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• 1998

The acute and subacute toxicity of New Wonbangwoohwangchungsimwon (NSCH) which was used l-muscone as substitutive material of musk were investigated in S.D. rats. In intraperitoneal acute toxicity test, rats were injected intraperitoneally with five dosages of 0, 500, 710, 1,000, 1,410 and 2,000 mg/kg. Body weights were significantly decreased at 500 and 710 mg/kg dose group in male and abnormal autopsy findings were founded in both sexes at all dose. Intraperitoneal $LD_{50}$ of NSCH was 1,088.3 mg/kg in male and 1159.3 mg/kg in female rats. In the subacute toxicity study, NSCH was administrated orally to both sexes of rats for 4 weeks as several doses(0, 320, 800, and 2,000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysis, and other findings. Above data strongly suggest that no observed adverse effect level of NSCH might be over 2,000 mg/kg/day in this study.

• Toxicological Research
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• v.14 no.2
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• pp.237-248
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• 1998

The acute and subacute toxicity of New Woohwangchungsimwon(NWCH) which was used l-muscone as substitutive material of musk were investigated in S.D. rats. In intraperitoneal acute toxicity test. rats(Sprague-Dawley, SPF) were injected intraperitoneally with dosages of 0, 540, 750, 1,070, 1.500 and 3,000 mg/kg. Body weights were significantly decreased at 540 mg/kg dose group in both sexes and abnormal autopsy findings were founded in both sexes at all treated groups. Intraperitoneal $LD_{50}$ of NWCH was 812.3 mg/kg in male and 872.3 mg/kg in female rats. In the subacute toxicity study, NWCH was administrated orally to both sexes of rats for 4 weeks as several doses(0, 320, 800 and 2, 000 mg/kg). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysis, and other findings. Above data strongly suggest that no observed adverse effect level of NWCH might be over 2,000 mg/kg/day in this study.