• Fisheries and Aquatic Sciences
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• v.4 no.4
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• pp.197-200
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• 2001

To investigate the re-treatment time of Microcotyle sebastis by oral administration of praziquantel, the residue levels of praziquantel in plasma of rockfish Sebastes schlegeli administered orally at a dose of 200 mg/kg B.W. were analyzed by reversed-phase HPLC, and the concentrations of praziquantel in the plasma were correlated with the extermination of M. sebastis. The absorption and depletion of praziquantel in the blood of rockfish were fast and the residual concentrations of praziquantel declined below $4\mu g/mL$ within 24 hr post treatment. Most of worms were exterminated within 3 hr after oral administration of praziquantel, however, a small number of M. sebastis were not killed by the treatment until end of the experiment. Considering fast drop of praziquantel in blood and extermination pattern of M. sebastis in the present results, retreatment at an interval of 9-12 hr would be effective for eradication of M. sebastis.

• 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.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.89-94
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• 2001

The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

• Journal of fish pathology
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• v.28 no.1
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• pp.43-51
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• 2015

The pharmacokinetic properties and residue levels of amoxicillin (AMOX) were studied after intramuscular injection to cultured olive flounders ($100{\pm}50g$), Paralichthys olivaceus. For pharmacokinetic studies, AMOX of 20 to 80 mg/kg body weight was administered at $17{\pm}2^{\circ}C$ or $22{\pm}2^{\circ}C$ and AMOX concentrations were determined in plasma, the liver, and the kidney by HPLC-UVD. Plasma samples were assessed at 0.25, 0.5, 1, 3, 6, 12, 24, 48, 72, 96, 168 hours post-dose, whereas liver and kidney concentrations were measured at 0.25 to 48 hours post-dose. The kinetic profiles of AMOX were analyzed by fitting to a 2-compartmental model with PKSolver program. The following parameters were obtained for a single dosage of 20, 40 and 80 mg/kg of body weight at $22^{\circ}C$ and 20 and 40 mg/kg of body weight at $17^{\circ}C$ in plasma, liver and kidney, respectively: $C_{max}$ (the peak concentration)= $27.23-257.36{\mu}g/m{\ell}$, $5.49-41.65{\mu}g/g$, $16.75-129.31{\mu}g/g$; $t_{max}$ (the time for peak concentration)= 0.05-0.91, 1.36-3.28, 1.95-4.49 h. For residue studies, AMOX of 40 and 400mg/kg was administered, and muscle samples were taken at 2, 5, 7, 14 and 21 days post-dose. The residueof AMOX in the muscle were found under the MRLs (maximum residue levels) within 7 days for the two doses.

• Journal of fish pathology
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• v.35 no.1
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• pp.93-102
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• 2022

This study performed a trichlorfon (TCF) residue and pharmacokinetic analysis with Japanese eels, Anguilla japonica, to obtain baseline data to establish the maximum residue level (MRL) of TCF in A. japonica. After dipping A. japonica in 30 ppm and 150 ppm of TCF at 28℃ and 18℃, drug residue in the body was analyzed with LC-MS/MS, and these results were further analyzed with the PK solver program to obtain the pharmacokinetic parameters of TCF in the serum, muscles, and liver. The maximum concentrations (C_max) in the serum, muscles, and liver were 25.87-357.42, 129.91-1043.73, and 40.47-375.20, respectively, and the time to maximum concentration (T_max) was 0.13-1.32h, 1.17-3.34h, and 0.14-5.40h, respectively. The terminal elimination half-life (T_1/2) was 2.13-3.92h, 5.30-10.35h, and 0.65-13.81h, respectively. In the 30 mg/L concentration group, TCF was not detected in the serum of eels 96 hours after bathing, and was below the detection limit after 336 hours in muscle and liver. On the other hand, in the 150 mg/L concentration group, TCF was not detected in the serum of eels 336 hours after bathing, but was detected in muscle and liver at 336 hours. In conclusion, the results of this study would be useful in establishing the MRL of TCF in farmed A. japonica.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.46-49
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• 2005

A simple HPLC method was employed for the determination of pentoxifylline in human serum. After addition of internal standard (IS, 50 uL of 3 ug/mL chloramphenicol methanol solution) into the serum sample, the drug and IS were extracted by dichloromethane. Following a 1-min vortex-mixing and a 15-min centrifugation at 3500 게m, the organic phase was transferred and evaporated to dryness under a vacuum. The residue was reconstituted with 120 ${\mu}L$ of mobile phase and 50 ${\mu}L$ was injected into C18 column with a mobile phase composed of 0.034 M phosphoric acid adjusted to pH 4 with 10 M NaOH and acetonitrile (75:25, v/v). The samples were detected using an ultraviolet detector at 273 nm. The method was simple, specific and validated with a limit of 10 ng/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 evaluated by analysis of human serum after oral administration of a single 400 mg dose to 8 healthy subjects. The pharmacokinetic parameters for pentoxifylline in human subjects were calculated using WinNonlin program. As a result, $AUC_{t},\;C_{max},\;T_{max}$ and $t_{1/2}$ were $962.28{\pm}645.69\;ng{\cdot}/mL$, $132.82{\pm}42.05$ ng/mL, $2.06{\pm}2.68$ hr and $8.74{\pm}4.38$ hr, respectively. Based on the results, this validated method appears to be useful fur the pharmnacokinetic study of pentoxifylline in humans.

• Fisheries and Aquatic Sciences
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• v.23 no.4
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• pp.10.1-10.10
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• 2020

Background: Butaphosphan (BTP) has recently been introduced into the Korean aquaculture sector as a stressattenuating agent. In this study, a sensitive chemical analytical method was established for the detection of BTP in the olive flounder (Paralichthys olivaceus) tissues. Methods: Utilizing a method employing liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), detection sensitivity, specificity, and precision were satisfactorily established. Temporal changes in the BTP plasma and muscle concentrations were assessed after a single intramuscular injection of BTP (50 and 150 mg/kg) to the olive flounder maintained at 13 ℃ or 22 ℃. Results: High BTP plasma levels were achieved immediately after the injection, and the drug was rapidly eliminated. Additionally, plasma BTP levels were markedly dependent on the elimination rate, which, in turn, seemed dependent on the water temperature, with the drug elimination half-life and mean residence time significantly shorter at 22 ℃ than 13 ℃. Overall, muscle BTP levels were markedly lower than the plasma levels. Notably, muscle levels were not influenced by water temperatures. Muscle BTP concentrations were used to estimate the necessary withdrawal period for drugs used in food fish, with BTP levels maintained far below the possible hazardous limit. Conclusions: In conclusion, the established LC-MS/MS method can be used for BTP residue detection with high sensitivity and reproducibility.

• Applied Biological Chemistry
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• v.40 no.2
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• pp.157-162
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• 1997

A novel compound, named YH-487, was synthesized by attaching the thiol and aminothiazole residue to $C_3$ and $C_7$ position of 7-aminocephalosporanic acid (7-ACA). The therapeutic efficacy on infected animals, pharmacokinetics in vivo and the effect on intestinal microflora of YH-487 were examined. The pharmacokinetics of YH-487 were similar to that of cefotaxime, a third generation ${\beta}-lactam$ antibiotics, in rat. Upon in vivo administration, YH-487 was predominantly delivered to kidney, and mostly excreted through kidney without making any metabolites. The therapeutic efficacy of YH-487 to animal infected with E. coli was three times and twenty times higher than that of cefotaxime and cefotiam, respectively, In vivo administration of YH-487 to Sprague-Dawley rats significantly decreased the population of intestinal gram negative species such as Enterobacteria and Barteroides. However, no significant changes were obseved in gram positive species such as Lactobacillus, Bifidobacteria and Staphylococcus. In addition, continuous administration of YH-487 did not increase the possibility to induce resistant strains in intestinal microflora.

• 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.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.53-58
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• 1997

$[Lys^7$]dermorphin, abbreviated K7DA, which has structural features similar to a metabolically stable $\mu$-opioid peptide agonist $[D-Arg^2, Lys^4$]dermorphin analogue (DALDA), but is intrinsically more potent with respect to binding to the $\mu$-opioid peptide receptor. The present studies report on attempts to enhance brain uptake of systemically administered K7DA by conjugation to a complex of streptavidin (SA) and the OX26 murine monoclonal antibody to the rat transferrin receptor, which undergoes receptor-mediated transcytosis through the blood-brain barrier (BBB). SA-OX26 conjugate mediates BBB transport of biotinylated therapeutics. The K7DA is monobiotinylated at the $\varepsilon$-amino group of the $[Lys^7$] residue with cleavable linker using NHS-SS-biotin. The brain uptake of $^{125}I$ labeled biotinylated K7DA ($^{125}I$-bio-SSa-K7DA) was very small and rapidly metabolized after intravenous injection. The brain uptake, expressed as percent of injected dose delivered per gram of brain, of the $^{125}I$-bio-55-K7DA bound to the SA-OX26 conjugate $^{125}I$-bio-SS-K7DA/SA-OX26) was 0.14$\pm$0.01, a level that is 2-fold greater than the brain uptake of morphine. The cleavability of the disulfide linker in vivo in rat plasma and brain was assessed with gel filtration HPLC and intravenous injection of labeled opioid chimeric peptides. The disulfide linker is stable in plasma in vivo but is cleaved in rat brain in vivo. In conclusion, these studies show that delivery of these potential opioid peptides to the brain may be improved by coupling them to vector-mediated BBB drug delivery system.