• Title/Summary/Keyword: half-dose

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Pharmacokinetics and tissue residues of ivermectin in swine

  • Park, Kwon-moo;Park, Jln-bong;Li, Long-hua;Han, Seong-kyu;Lee, Hye-sook;Park, Jong-myung;Chang, Byoung-sun;Lee, Mun-han;Ryu, Pan-dong
    • Korean Journal of Veterinary Research
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    • v.39 no.2
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    • pp.257-266
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    • 1999
  • Ivermectin is a widely used broad spectrum antiparasitic agent in veterinary medicine. In this work, we examined the pharmacokinetic parameters and the tissue residue profile of a new injectable formulation of ivermectin developed for pigs. The plasma ivermectin levels reached the peak at about 9 and 2 hours after the administrations in young and adult pigs, respectively. But the elimination half-life (3-3.5 days) and the $C_{max}$ values (24~28 ng/ml) were not significantly different between young and adult pig groups. When compared to the reference formulation, the $C_{max}$ of test formulation was higher and $T_{1/2}$ values were shorter than those of the reference formulation, respectively. The tissue residue levels were dose- and time-dependent and were higher in the liver and fat, than in the other tissues such as the injection sites, the kidney, intestine, muscle, plasma (4~74 ng/g) at the 7th day after the administration of both formulations of ivermectin. Then, the mean tissue ivermectin levels at the 21st day after the administration in all the tissues decreased to 7.4 and 25% of the 7th day levels in the test and reference formulations, respectively. In general, the tissue levels of ivermectin in the animals treated with the test formulation decreased more rapidly than those with the reference formulation. The tissue to plasma distribution ratio (T/P ratio) of ivermectin was higher in the liver and fat than other tissues. The T/P ratio in the liver of animals treated with the test formulation was somewhat higher than that in the animals treated with the reference formulation. Taken together, the results of pharmacokinetic and tissue residue studies indicate that the test formulation of ivermectin for subcutaneous injection is comparable to the reference formulation, but unique in that it has higher peak plasma concentrations, shorter elimination half-life and higher T/P ratio in the liver than the reference formulation.

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Effects of Combined Application of Rice Bran and Chemical Fertilizer on the Phytochemical Contents of Rice

  • Kang, Mi-Young;Kim, Joo-Hee;Heo, Kyu-Hong;Cho, Sun-Shik;Esguerra, Manuel Q.;Rico, Cyren M.;Son, Tae-Kwon;Lee, Sang-Chul
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.53 no.spc
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    • pp.65-71
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    • 2008
  • The effect of rice bran (RB) applied alone or in combination with chemical fertilizer at different application rate on the phytochemical and antioxidant properties of rice was investigated. The treatments were 3 levels of RB namely: 200% RB (500 kg $10a^{-1}$), 100% RB (250 kg $10a^{-1}$), 50% RB (125 kg $10a^{-1}$), Recommended fertilizer dose (RF: $N-{P_2}{O_5}{K_2}O$, 11-5.5-4.8 kg $10a^{-1}$) combined with each RB, Half-recommended fertilizer dose (HRF: $N-{P_2}{O_5}{K_2}O$, 5.5-2.75-2.4 kg $10a^{-1}$) combined with each RB, RF and HRF applied at 1, 5, 10 days before rice transplanting (DBT). The parameters investigated were antioxidant, phytosterol and fatty acid contents. Results showed that the antioxidant property and phytosterol contents were high at 10 DBT HRF plus RB, 5 DBT RF plus RB, and 1 DBT 100 and 200% RB. However, total polyphenols increased from 10 to 1 DBT. In the case of fatty acids, no general trend was observed between treatments at different application times. Linoleic acid was high at 10 DBT HRF plus RB while linolenic acid was not affected at different application times. Palmitoeic and oleic acids were not also affected at 5 and 10 DBT. Saturated fatty acids were not also affected by any treatment at different application times except for palmitic acid.Most parameters obtained higher values at 100 and 200% RB treatments in 1 DBT.

Effects of Alcohol on Neurocognitive Function, Psychomotor Performance and Subjective Response in Koreans with Different ALDH2 Genotypes (한국인에서 Aldehyde Dehydrogenase 2 유전자 변이가 알코올의 신경인지 기능, 정신운동성 수행 및 주관적 반응에 미치는 영향)

  • Shin, Il-Seon;Yoon, Jin-Sang;Kim, Hyun;Yoon, Bo-Hyun;Lee, Hoon;Jung, Jae-Sung;Lee, Hyung-Yung
    • Korean Journal of Biological Psychiatry
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    • v.6 no.2
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    • pp.176-188
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    • 1999
  • Objective : The purpose of this study was to evaluate the effects of alcohol on neurocognitive function, psychomotor performance and subjective response in healthy Korean adults with different ALDH2 genotypes. Method : A total of 24 males, half with active $ALDH2^*1/2^*1$ and the other with inactive $ALDH2^*1/2^*2$, was selected through genotyping using restriction fragment length polymorphism. In a double-blind, placebo-controlled cross-over design, each subject consumed 0.5g/kg dose of alcohol, given as a mixture of 40% vodka and orange juice, and placebo(orange juice) on two separate occasions on an average of weekly intervals. The blood alcohol concentrations(BACs) were measured using a breath analyzer at baseline and at 30, 60 minutes after drinking. P300s were measured at baseline and at 30 minutes after alcohol and placebo intake. Vital signs and psychomotor performance[Critical Flicker Fusion Threshold(CFFT), Choice Reaction Time (CRT), Digit Symbol Substitution(DSS)] were measured at baseline and at 60 minutes after alcohol and placebo intake. Subjective responses were measured at the end of the study. The statistical analysis focused on whether there were any differences between groups with different ALDH2 genotypes. Results : The major results are as follows. 1) BACs in the inactive group were overall equivalent to those in the active group. Only in terms of time, BACs were significantly higher overall at 30 minutes than at 60 minutes after alcohol intake. 2) Pulse rates were significantly increased after alcohol intake compared with placebo, and the increase was greater in the inactive than in the active group. 3) P300 latencies in leads Fz(frontal), Cz(cental) and Pz(parietal) were significantly increased after alcohol intake compared to placebo, and the increase was greater in the inactive than in the active group. P300 amplitudes in leads Cz and Pz were significantly decreased overall after alcohol intake compared to placebo. 4) Compared with placebo, alcohol produced significant effect on the psychomotor performance : impairment in the inactive group, improvement in the active group. 5) Compared with placebo, alcohol significantly induced a negative or an intense effect on the subjective responses in the inactive group, but little negative and even a somewhat positive effect in the active group. Conclusions : These results suggest that ALDH isozyme variance might be an important factor to determine the effects of acute dose of alcohol on the various psychobehavioural functions and also to determine the alcohol use pattern and to predict the future development of alcohol overuse and/or abuse.

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Assessment of Vibration Produced by the Grinder Used in the Shipbuilding Industry and Development of Prospective Prevalence Model of Hand-arm Vibration Syndrome (선박건조업에서 사용되는 그라인더의 진동평가와 수지진동증후군 예측 모델 개발)

  • Yim, Sanghyuk;Lee, Yunkeun;Park, Hee-Sok
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.16 no.4
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    • pp.398-412
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    • 2006
  • The purpose of this study is to investigate the relationship between the acceleration of vibration by the powered hand tools used in the shipbuilding industry, and to develop the prospective prevalence model for the hand-arm vibration syndrome among the shipbuilding workers.The acceleration levels and frequencies of six types of grinder were measured using the ISO5349 method along with the time of exposure to the vibration from the powered hand tools. Medical examination for 114 workers were performed using the cold provocation test. Comparisons were made between the estimated prevalence of hand-arm vibration syndrome from ISO5349 and the observed values from the medical examinations. By multiple regression, we developed the prospective prevalence model of hand-arm vibration syndrome produced by the hand tools used in the shipbuilding industry. 4 hour-energy-equivalent frequency-weighted accelerations were $6.23m/s^2$ in the grinding job done after welding, and $13.39m/s^2$ in the grinding job done before painting. The mean exposure time while holding powered hand tools was 4.64 hours. Prevalence rates of Raynaud's Phenomenon were 12.04% in the grinding after soldering, and 42.9% in the grinding before painting measured using the ISO5349 method. After exposure to vibration for 10.79 years, about a half of the workers in the grinding after welding could developed Raynaud's Phenomenon. For the workers in the grinding before painting, the latency was 5.02 years. The ISO equation for dose response relationship was not significantly correlated with observed recovery rates of finger skin temperatures, blood flows and amplitudes of nerve conduction velocities. A multiple regression model for dose-response relationship was proposed from the results. Recovery rate of the skin temperatures = -0.668+ 0.337 ${\times}$ 4 hour energy equivalent frequency-weighted accelerations + 0.767 ${\times}$ duration of vibration exposure(years) The validity was proved by multiple regression analysis after correlation transformation and regression results based on model-building data and validation data.

Isolation, Root Colonization and Evaluation of Some Plant Growth-promoting Rhizobacteria in Paddy Rice

  • Kang, Ui-Gum;Park, Hyang-Mi;Ko, Jee-Yeon;Lee, Jae-Saeng;Jeon, Weon-Tai;Park, Chang-Young;Park, Ki-Do;Chebotar, Vladimir K.
    • Korean Journal of Soil Science and Fertilizer
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    • v.50 no.3
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    • pp.135-149
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    • 2017
  • In order to obtain promising rice growth-promoting microbial strains that can be used as substitutes for chemical fertilizers, 172 bacterial strains were isolated from rice roots grown in Korean and Russian soils. Out of them, the strains KR076, KR083, KR181 and RRj228 showed plant growth-promoting activities on maize seedlings. Bacillus megaterium KR076 and Bacillus sp. KR083 showed both nitrogen-fixing and plant growth-promoting activities, while Rhizobium sp. KR181 and Pseudomonas sp. RRj228 appeared to support only plant growth-promotion, but not $N_2$ fixation. Especially, RRj228 showed high growth promoting activity at low concentrations. Inoculation studies with KR083 and RRj228 revealed a high affinity to the Japonica rice variety such as Junambyeo than the Korean Tongil type variety such as Arumbyeo. Both KR083 and RRj228 strains showed rhizoplane and/or endophytic colonization in Japonica and Tongil types rice when soaked with the bacterial suspension of $1.1{\times}10^5cfu\;ml^{-1}$ for six and twelve hours. However, the total bacterial cell numbers were higher in the roots of Japonica variety than in the Tongil type. In inoculation trials with Daesanbyeo rice variety, the seedlings inoculated with KR181 and RRj228 at the rate of $2.0{\times}10^6cfu\;ml^{-1}$ showed yield increment of 35% and 33% (p < 0.01), respectively, so that they contributed to the replacement of chemical fertilizer at half doses of N, $P_2O_5$, and $K_2O$ in pots. In Junambyeo rice seedlings, the strain RRj228, when inoculated with a cell suspension of $1.8{\times}10^6cfu\;ml^{-1}$, promoted 3.4% higher yield at 70% dose than at a full dose level of N $110kg\;ha^{-1}$ in field. These results suggest that the rhizobacteria KR181 and RRj228 are prospective strains for enhancing rice performance.

Determination of Ethambutol n Human Plasma by a Validated HPLC Method and Its Application to Single-dose Pharmacokinetics (인체혈장 중 에탐부톨의 HPLC 분석법의 검증 및 단일용량 투여에 의한 약물동태 연구)

  • Gwak, Hey-Sun;Park, Kyung-Ho;Choi, Jun-Shik;Song, Gin-A;Sung, Min-Kyung;Jang, Jung-Ok;Lee, Hwa-Jeong
    • Journal of Pharmaceutical Investigation
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    • v.35 no.2
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    • pp.123-127
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    • 2005
  • An HPLC method was employed for the determination of ethambutol in human plasma. After addition of internal standard (IS, octylamine, $2\;{\mu}g/mL$) and alkalinization of the plasma with 5 M sodium hydroxide, the drug and IS were extracted into the mixture of chloroform and diethyl ether (40:60, v/v). Following a 15-min vortex-mixing and a 10min centrifugation, the organic phase was spiked with $100{\mu}L$ of phenylethylisocyanate $(2000{\mu}g/mL)$ for chemical derivatization, mixed for 5 min and evaporated to dryness under a stream of nitrogen. The residue was reconstituted with $100{\mu}L$ of mobile phase and $20{\mu}L$ was injected into C18 column with a mobile phase consisting of methanol:water (70:30, v/v). The samples were detected utilizing an ultraviolet detector at 200 nm. The method was specific and validated with a limit of $0.15\;{\mu}g/mL$. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of this method was demonstrated by analysis of human plasma after oral administration of a single 1200-mg dose to 20 healthy subjects. From the plasma ethambutol concentration vs. time curves, the mean AUC was $9.61{\pm}1.64\;{\mu}g{\cdot}hr/mL$ and Cmax of $2.68\;{\mu}g/mL$ reached 2.73 hr after administration. The mean biological half-life of ethambutol was $3.46{\pm}1.21$ hr. Based on the results, this simple and validated assay could readily be used in any pharmacokinetic studies using humans.

ATP-Sensitive $K^+$ Currents in Gastric Myocytes Isolated from Guinea-pig

  • Jun, Jae-Yeoul;Yeum, Cheol-Ho;Yun, Pyung-Jin;Park, Jong-Seong;Kim, Sung-Joon;So, In-Suk;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.1
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    • pp.85-93
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    • 1998
  • ATP-sensitive $K^+$ channels ($K_{ATP}$) were not identified in gastric smooth muscle cells. However, in tension recording of intact gastric circular muscle, lemakalim of $K_{ATP}$ channels opener in other tissues suppressed mechanical contractions and this effect was blocked by glibenclamide, a specific inhibitor of $K_{ATP}$ channels. The aims of this study were to investigate whether $K_{ATP}$ channels exist in gastric smooth muscle of guinea-pig and to know its physiological role. Whole cell $K^+$ currents activated by lemakalim were recorded from freshly isolated cells with a 0.1 mM ATP, 140 mM KCl pipette solutions. Lemakalim (10 ${\mu}M$) increased inward currents of $-224{\pm}34$ pA (n=13) at -80 mV of holding potential in bath solution contained 90 mM $K^+$. Bath-applied glibenclamide (10 ${\mu}M$) inhibited the lemakalim-activated inward currents by $91{\pm}6%$ (n=5). These lemakalim-activated inward currents were reduced by increased intracellular ATP from 0.1 to 3 mM ($-41{\pm}12$ pA) (n=5). The reversal potential of the glibenclamide- sensitive inward currents was $-5.2{\pm}2.4$ mV (n=3) in external 90 mM $K^+$ and shifted to $-14.8{\pm}3.6$ mV (n=3) in external 60 mM $K^+$, which close to equilibrium potential of $K^+$ ($E_K$). External barium and cesium inhibited the lemakalim-activated inward currents dose-dependently. The half-inhibitory dose ($IC_{50}$) of barium and cesium were 2.3 ${\mu}M$ (n=5) and 0.38 mM (n=4), respectively. 10 mM tetraethylammonium (TEA) also inhibited the lemakalim-activated inward currents by $66{\pm}15%$ (n=5). Both substance P (SP) (5 ${\mu}M$) and acetylcholine (ACh) (5 ${\mu}M$) inhibited lemakalim-activated inward currents. These results suggest that $K_{ATP}$ channels exist in the gastric smooth muscle and its modulation by neurotransmitters may play an important role in regulating gastric motility.

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Pharmacokinetics and Lymphatic Delivery of Oligopeptide after Intramuscular Injection of Oligopeptide-bearing Liposomes to Rats (흰쥐에서 올리고펩타이드 함유 리포솜의 근육주사후 체내동태 및 임파이행)

  • Shin, Dae-Hwan;Cho, Byung-Suk;Choi, Kyu-Seok;Song, Suk-Gil;Lee, Chong-Kil;Chung, Youn-Bok
    • Journal of Pharmaceutical Investigation
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    • v.38 no.3
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    • pp.191-197
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    • 2008
  • The purpose of the present study was to examine the pharmacokinetics and lymphatic delivery of the oligopeptide, a model peptide of X antigen epitope peptides, after the intramuscular administration of the peptide-bearing liposomes in rats. $^{14}C$-labelled peptide was used as a tracer to analyze the peptide levels in plasma, bile, urine, tissue homogenates, and lymph nodes (superior cervical nodes, brachial nodes and superior mesenteric nodes). Model peptide rapidly disappeared from the plasma by 30 min (${\alpha}$ phase) after i.v. administration, which was followed by the late disappearance. The apparent plasma half-lives ($t_{1/2({\alpha}),app}$) of the peptide at the ${\alpha}$ phase when administered at a dose of 0.2-1.0 mg/kg were about 5 min. The maximum plasma concentration ($C_{max}$) was $1.52\;{\mu}g/mL$, after the i.m. administration of the peptide at a dose of 1.0 mg/kg. The bioavailability, which was calculated from the time zero to last quantitative time, of the i.m. administered peptide was over 60%. Of the various tissues tested, the peptide was mainly distributed in the kidney after the i.m. administration. The peptide levels in the kidney 3 hr after the i.m. administration were higher than those of maximum plasma concentration ($C_{max}$). The cumulative amounts of the peptide found in the urine 72 hr after the administration of 1.0 mg/kg were 2-folder higher than those in the bile, suggesting that the peptide is mostly excreted in the urine. Moreover, the concentrations of the peptide in the lymph nodes were as high as that of the plasma and the tissues. In conclusion, the peptide concentration in the lymph nodes was maintained by 24 hr after the i.m. administration of the peptide-bearing liposomes.

Residual Characteristics of Etofenprox and Methoxyfenozide in Chinese Cabbage (Etofenprox와 Methoxyfenozide의 배추 중 잔류특성)

  • Lee, Eun-Young;Noh, Hyun-Ho;Park, Young-Soon;Kang, Kyung-Won;Kim, Joo-Kwang;Jin, Yong-Duk;Yun, Sang-Soon;Jin, Chung-Woo;Han, Sang-Kuk;Kyung, Kee-Sung
    • The Korean Journal of Pesticide Science
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    • v.13 no.1
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    • pp.13-20
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    • 2009
  • Two insecticides, commonly used for Chinese cabbage, etofenprox and methoxyfenozide, were subjected to a field residue trial to evaluate safeties of the residues at harvest. The pesticides were sprayed onto the crop at recommended and double doses 10 days before the prearranged harvest and then sampling was done at 0, 1, 2, 3, 5, 7, 10, and 12 days after spraying. The amounts of pesticides residues in the crop were analyzed by chromatographic methods. Limits of detection (LODs) of both etofenprox and methoxyfenozide were $0.01mg\;kg^{-1}$ and mean recoveries were $96.76{\pm}2.67$ (CV=2.76%) and $95.84{\pm}2.57%$(CV=2.69%) in case of etofenprox and $103.26{\pm}3.21$ (CV=3.11%) and $94.50{\pm}1.35%$(CV=1.43%) in case of methoxyfenozide, respectively. Biological half-lives of etofenprox and methoxyfenozide were 3.2 and 3.5 days at the recommended dose and 2.7 and 3.5 days at the double dose, respectively. Initial residue levels of the pesticides at the recommended and double doses exceeded their MRLs, but final residue levels of the pesticides in the crop samples at harvest were less than their MRLs. The ratios of the EDI to ADI by intake the crop harvested 10 days after spraying were less than 4% of their ADIs, representing that residue levels of two pesticides at harvest were evaluated as safe.

Removal Characteristics of Synthetic Musk Compounds in Water by Ozone Treatment (오존처리에 의한 수중의 인공 사향물질 제거특성)

  • Seo, Chang-Dong;Son, Hee-Jong;Yoom, Hoon-Sik;Lee, Sang-Won;Ryu, Dong-Chun
    • Journal of Korean Society of Environmental Engineers
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    • v.34 no.2
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    • pp.73-78
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    • 2012
  • In this study, three different synthetic musk compounds (SMCs) in the Nakdong river water (raw water) and rapid sand filtered water were treated by $O_3$ process. The experimental results showed that the removal efficiency of musk ketone (MK) was lower than removal efficiency of AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) and HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[c]-2-benzopyran) for both the raw water and the rapid sand filtered water. And in general, the removal efficiencies of three SMCs in the raw water were lower than that in the sand filtered water. Under the $O_3$ dose of 0.5~10.0 mg/L, the removal rate constants (k) of three SMCs for the raw and sand filtered waters increased rapidly with the increased $O_3$ dose. In the case of drinking water treatment plants (DWTPs) which were selected pre- and post-$O_3$ processes (located in the downstream of Nakdong River), operation conditions of pre- and post-$O_3$ process were $0.5{\sim}2.0mg{\cdot}O_3/L$ (2~4 min) and $0.5{\sim}2.5mg{\cdot}O_3/L$ (6~8 min). Therefore, $O_3$ doses and contact times of same conditions with above were very difficult to remove SMCs in DWTPs.