• Title/Summary/Keyword: 90 day repeated dose toxicity

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Effect of Gongjindan, a Traditional Korean Polyherbal Formula, on the Pharmacokinetics Profiles of Donepezil in Male SDRats (2) - Single Oral Combination Treatment of Donepezil 10mg/kg with Gongjindan 100mg/kg, 1.5hr-intervals with 7-day Repeated Treatment -

  • Kwon, Oh Dae;Chung, Dae-Kyoo;Park, Soo Jin;Lee, Young Joon;Ku, Sae Kwang
    • 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.

A 90-day Safety Study (Repeated-Dose Oral Toxicity Study) of Genetically Modified ${\beta}$-Carotene Biofortified rice in Sprague-Dawley Rats (SD 랫드에서 베타카로틴강화미의 90일 반복투여 경구독성시험)

  • Park, Soo-Jin;Jeong, Mi-Hye;Lee, Si-Myoung;Kim, Mi-Kyoung;Park, Kyung-Hun;Park, Jae-Yup
    • The Korean Journal of Pesticide Science
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    • v.15 no.3
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    • pp.278-288
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    • 2011
  • This study was conducted to evaluate the safety of ${\beta}$-carotene biofortified rice, a genetically modified organism (GMO) developed by Rural Development Administration. ${\beta}$-carotene biofortified rice were exposed on Sprague-Dawley rats for 13 weeks. All rats survived until the end of the exposure period. There were no biologically significant differences in body weight, feed and water consumption, weight gains and feed efficiency. There were no clinical signs of toxicity attributable to exposure to GM rice. Mild decreases in AST, ALT, TG levels were observed in Group II (25% GM rice (w/w) and Group III (50% GM rice (w/w), both in females and males. Results of histopathological changes treated with the ${\beta}$-carotene biofortified rice had no significant differences between the control and treatment groups. Based on these results, we deemed that genetically modified ${\beta}$-carotene biofortified rice was as safe as conventional rice.