Kim, Choong-Yong;Heo, Jeong-Doo;Han, Su-Cheol;Jo, Yeong-Woo;Chung, Moon-Koo
Proceedings of the Korean Society of Toxicology Conference
/
2002.11b
/
pp.194-194
/
2002
Interferon has therapeutic potential for a wide range of infectious and proliferous disorders such as chronic hepatitis C. However, it has drawbacks such as relatively short serum half-life and rapid clearance like other therapeutic proteins. The attachment of a polyethylene glycol (PEG) moiety to interferon is considered as one of the most promising solutions for its ability to extend the plasma residence time.(omitted)
The metabolism of dromostanolone (2α-methyl-5α- androstan-17β-ol-3-one) was studied in three adult volunteers after oral dose of 20 mg. Solvent extracts of urine obtained after enzyme hydrolysis were derivatized with MSTFA/TMCS and MSTFA/TMIS. The structures of intact drug and its metabolites were determined by gas chromatography/mass spectrometry (GC/MS) in electron impact (EI) mode. The major metabolite (2α-methyl-5α- androstan-3α-ol-17-one), its 3β-epimer, parent compound, and several hydroxylated metabolites including intact drug were detected by comparing total ion chromatograms of control urine with that of the administered sample. Two epimers of 2α-methyl-5α- androstan-3,17β-diol were detected using selected ion monitoring. The maximum excretion of dromostanolone and 2α-methyl-5α- androstan-3α-ol-17-one was reached in 6.2-15 hr. The half-life of intact dromostanolone was 5.3 hr. About 3.0% of the administered amount was found to be excreted within 95 hr as unchanged form.
Toxicity of $Ni^{2+}$ and Tebuconazole were investigated via FETAX (Frog Embryo Teratogenesis Assay-Xenopus) protocol using domestic frog embryos. Embryos of Black-spotted pond frog, Rana nigromaculata, were incubated and toxic effects of $Ni^{2+}$ and Tebuconazole were investigated by probit analysis. As a result, mortality and malformation rates were increased and larval body length was decreased in a dose dependant manner of $Ni^{2+}$ and Tebuconazole. The half maximal effective concentration ($EC_{50}$) of $Ni^{2+}$ and Tebuconazole were 0.07, $12.7mg\;L^{-1}$, respectively and the half maximal lethal concentration ($LC_{50}$) of $Ni^{2+}$ and Tebuconazole were 4.2, 39.1, respectively. The teratogenic index (TI) were 61.4 in $Ni^{2+}$ and 3.1 in Tebuconazole, respectively. These results reveals that $Ni^{2+}$ and Tebuconazole suppress the development of Black-spotted pond frog embryos at the low concentration as showing teratogenic effects in other assay system. Therefore, teratogen assay system using the Rana nigromaculata embryos could be useful as a tool to evaluate the toxicity of the pollutants in environment.
Park, Hee-Dong;Kim, Hee-Jin;Oh, Yeong-Soo;Kim, In-Chull;Kim, Yong-Zu;Koh, Hyun-Chul;Shin, In-Chul;Lee, Yong-Hee;Lee, Chang-Ho
Archives of Pharmacal Research
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v.26
no.3
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pp.224-231
/
2003
The anti-thrombotic effects of LB30057, a direct thrombin inhibitor, were evaluated with in vivo rat and dog thrombosis models. In rats, 1 mg/kg of LB30057 inhibited half of the clot formations in the inferior vena cava at 5 minutes after intravenous application. When measured at 2 hours after oral application, 100 mg/kg prevented approximately half of the clot formations in the inferior vena cava and 50 mg/kg prolonged the mean occlusion time from $15.6{\pm}1.3$ minutes to $47.2{\pm}8.3$ minutes in the carotid artery. In dogs, the formation of thrombus in the jugular vein was reduced to half at a dose range of 20-30 mg/kg at 6 hours after oral application. In addition, the LB30057 dosage required to reduce venous clot formation by approximately 80-90% in dogs was only about 10% of that required for the same reduction in rats. This is probably due to the variation in its time-dependent blood concentration profiles in each species; for example, the plasma half-life of LB71350 in dogs was longer than that in rats ($153.0{\pm}3.0$ vs. $129.7{\pm}12.7$ min at 30 mg/kg, i.v., respectively). AUG, $T_{max},{\;}G_{max}$, and BA in dogs were 59, 8.9, 9.17, and 13.3 times higher than those in rats at oral 30 mg/kg, respectively. Taken together, these results suggest that LB30057 administered orally is effective in the prevention of arterial and venous thrombosis in rats and dogs. It therefore represents a good lead compound for investigations to discover a new, orally available, therapeutic agent for treating thrombotic diseases.
BACKGROUND: The present study was carried out to identify the residue patterns of insecticide pyridalyl and fungicide fluopicolide in watermelon and calculate the biological half-lives for establishing the pre-harvest residue limits (PHRLs). METHODSANDRESULTS:The watermelon samples for residue analysis were harvested 7 times during 0~10 days (Field 1) and 0~20 days (Field 2) after treatment of pesticides on watermelon in two different fields at the recommended dose, respectively. The residue analysis was conducted with HPLC/UVD. The method limit of quantitation (MLOQ) were set at 0.05 and 0.02 mg/kg, respectively, and overall mean recoveries were 81.2~90.5% for pyridalyl and fluopicolide. The residues in sample were stable for 43~47 days. The initial residue amount in field 1 and 2 were 0.12~0.16 mg/kg for pyridalyl and 0.23~0.24 mg/kg for fluopicolide, which were below maximum residue limit (MRL). The biological half-lives in field 1 and 2 were 26.9 and 17.9 days for pyridalyl and 16.6 and 94.2 days for fluopicolide, respectively. CONCLUSION: The PHRL for watermelon were estimated as 0.21 and 1.03 mg/kg for pyridalyl and flopicolide at 10 days before harvesting. The residue patterns of pyridalyl and fluopicolide were characterized by a very slow decrease of residue levels in watermelon.
An investigation of the effects of Pb for domestic anuran embryos were evaluated with the Frog Embryo Teratogenesis Assay; Xenopus (FETAX). Depending on the species, the difference between the embryo size and the embryonic development time was determined. As a result, mortality and malformation rates were increased, malformation patterns were changed and larval body length were decreased in a dose dependent manner of the Pb. The half maximal lethal concentration ($LC_{50}$) of the Bufo gargarizans, Hyla japonica, Rana nigromaculata and Bombina orientalis were 0.58, 0.49, 0.52, $0.54mg\;L^{-1}$, respectively. The half maximal effective concentration ($EC_{50}$) of the Bufo gargarizans, Hyla japonica, Rana nigromaculata and Bombina orientalis were 0.35, 0.74, 0.30, $0.29mg\;L^{-1}$, respectively. The teratogenic index (TI) were 1.66 in the Bufo gargarizans, 1.81 in the Hyla japonica, 1.73 in the Rana nigromaculata and 1.86 in the Bombina orientalis, respectively. Therefore, the Pb seems likely to have a teratogenic effect in all four species' embryonic development. The Bombina orientalis was the most sensitive to the Pb. This means that the difference between the different species, even if they have all been exposed to the same concentration of pollutants depending on the species. The result above show that the Pb acts as a teratogenic agent in the development of the four domestic frog species.
The Journal of Korean Society for Radiation Therapy
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v.24
no.2
/
pp.197-203
/
2012
Purpose: In this study, we considerate our radiation therapy process for the breast cancer patient implanted a pacemaker applying the machine movement surgery, shielding, beam selection. Materials and Methods: We perform radiation therapy to a 54 years old, breast cancer patient implanted a pacemaker. The patient underwent a surgery to move the position of a pacemaker to right side breast after consultation with cardiology department. Prescribed dose was 5,040 cGy and daily dose 180 cGy for 28 fractions. The 10 MV photon energy, field size 0/$9.5{\times}20$ cm, half beam and opposing portal irradiation are used. To find out appropriate thickness of shielding board, we carried out an experiment using a solid water phantom ($30{\times}30{\times}7$ cm), a Farmer-type chamber (TN30013, PTW, Germany) and a shielding board (Pb $28{\times}27{\times}0.1$ cm). We calculated expected absorbed dose to te pacemaker with absorb ratio and shielding ratio. In the PTP system (Eclipse, Varian, USA), we figured out how much radiation would be absorbed to the machine with and without shielding. First day of the radiation therapy, we measured head scatter to the pacemaker with MOSFET Dose Verification System (TN-RD-70-W, Medical Canada Ltd., Canada). Results: In the phantom measurement, we found out appropriate thickness was 2 mm of shielding board. In the RTP, when using 2 mm shielding the pacemaker will be absorbed 11.5~38.2 cGy and DVH is 77.3 cGy. In the first day of the therapy, 4.3 cGy was measured so 120.4 cGy was calculated during total therapy. The patient was free from any side effects, and the machine also normally functioned. Conclusion: As the report of association which have public confidence became superannuated, there is lack of data about new machine. We believe that radiation therapy to thiese kind of patients could be done successfully with co-operation, patient-suitable planning, accurate QA, frequent in-vivo dosimetry and monitoring.
Choe, Jae Young;Jang, Kyung Mi;Hwang, Young Ju;Choi, Bong Seok;Park, Jong Kwang;Yoon, Young Ran;Kim, Chan Duck;Cho, Min Hyun
Childhood Kidney Diseases
/
v.18
no.1
/
pp.18-23
/
2014
Purpose: The pharmacokinetics of tacrolimus, one of the most widely used immunosuppressive drugs, are known to vary by sex, age, and ethnicity during pediatric transplantation. This study assessed the pharmacokinetic characteristics and associated factors of tacrolimus in Korean children receiving a kidney transplant. Methods: We retrospectively reviewed the pharmacokinetic data (therapeutic dose, trough level, clearance, and half-life) of 9 children who were given tacrolimus as one of their initial immunosuppressive drugs after kidney transplantation. In addition, we compared the findings to data from 10 adult kidney transplant recipients. Results: The mean age of our pediatric patients was 13.9 years, and the maleto- female ratio was 4:5. The mean dose of tacrolimus was $0.19{\pm}0.14$ mg/kg/day. The mean dose of tacrolimus for males was $0.23{\pm}0.12$ mg/kg/day, which was significantly higher than the dose for females ($0.16{\pm}0.14$ mg/kg/day). The trough level was not significantly different between both groups. The clearance rate of tacrolimus for males was also significantly higher than females. Although the dosage of tacrolimus for patients over the age of 12 years was lower ($0.18{\pm}0.13$ vs. $0.21{\pm}0.16$ mg/kg/day) and the trough level was higher ($8.2{\pm}4.5$ vs. $7.2{\pm}4.2$ mg/mL) than that for patients under the age of 12 years, there was no significant difference between them. However, there were significant differences between children and adults in dose, clearance, and half-life of tacrolimus. Conclusion: Out study suggests that the pharmacokinetics of tacrolimus tends to vary with sex and age. Therefore, large-scale prospective studies are required to verify the proper therapeutic dosage of tacrolimus in Korean children.
Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.
Background : Since up to 90% of a theophylline dose is biotransformed, probably by interaction with one or more the variants of the cytochrome P-450 drug metabolism system, anti-tuberculosis agents including drugs influencing microsomal enzyme systems, such as isoniazid and rifampicin. may be affect the elimination of theophylline. Method : The effect of combination therapy with isoniazid(INH), rifampicin(RFP), ethambutol(EMB) and pyrazinamide(PZA) on the pharmacokinetics of theophylline was evaluated by a computer program using Bayesian method. Three group were divided as follows. Group I is control, Group II is treated with INH. RFP, EMB and PZA and Group III is treated with INH, RFP and EMB. All of them were ilon-smoker who were normal in liver and renal functions, and not administered drugs affecting on the clearance of theophylline with exception of anti-tuberculous agents. Results : When it compared control with test groups, the clearance of theophylline in Group II and Group III was significantly decreased(p<0.001), and half life in Group II and Group III showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group II and Group III. Conclusion : These results suggest that theophylline dose may be need of readjustment in concurrent medication of anti-tuberculous agents including INH, RFP, and EMB.
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