• Journal of Fisheries and Marine Sciences Education
• /
• v.28 no.3
• /
• pp.692-700
• /
• 2016

This study was aimed at investigating the residual patterns of thiamphenicol (TP) in the cultured olive flounder (Paralichthys olivaceus) and black rockfish (Sebastes schlegeli) following oral administration. TP concentration were detected by high performance liquid chromatography with UV detector. The recovery rates of TP in serums ranged 77.05~97.23% (olive flounder) and 89.96~97.11% (black rockfish) for the concentration of 0.1, 1.0, $10{\mu}g/mL$, respectively. After single administration of TP (100 mg/kg body weight) by oral route in olive flounder ($700{\pm}50g$, $23{\pm}1.5^{\circ}C$) and black rockfish ($500{\pm}30g$, $23{\pm}1.5^{\circ}C$), the concentration in the serum was determined at 1, 5, 10, 15, 24, 30, 50, 168, 264 and 432 h post-dose. Two-compartment model was applied to analyze in the pharmacokinetics of TP administered to the fishes. In the serum of olive flounder, TP was detected on 10 and 15 hours after treatment were $10.08{\mu}g/mL$ and $10.06{\mu}g/mL$ as maximum level, respectively. In the serum of black rockfish, TP was detected on 15 hours after treatment were $8.88{\mu}g/mL$ as maximum level. Concentrations of TP to the fishes were not measurable at 432 hours (18 days) after treatment in all samples. Similar residual patterns of TP were revealed between the fishes. These results are helpful for estimating withdrawal time of TP which has been already in use for farmed fish treatment.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.1
• /
• pp.45-51
• /
• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of dipyridamole in human serum was developed, validated, and applied to the pharmacokinetic study of dipyridamole. Dipyridamole and internal standard, loxapine, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Nova Pak $C_{I8}$ column with the mobile phase of 40 mM ammonium acetate:methanol:acetonitrile (35:35:30)(v/v/v, pH 7.8). Detection wavelength of 280 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed dipyridamole concentration (50 ng/mL) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 2-2000 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 2 ng/mL, which was sensitive enough for pharmacokinetic studies of dipyridamole. The overall accuracy of the quality control samples ranged from 103.94 to 105.86% for dipyridamole with overall precision (% C.V.) being 4.60-11.49%. The relative mean recovery of dipyridamole for human serum was 97.64%. Stability studies showed that dipyridamole was stable during storage, or during the assay procedure in human serum. The peak area and retention time of dipyridamole were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of dipyridamole in human serum samples for the pharmacokinetic studies of orally administered Dimor tablet (75 mg as dipyridamole) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.1
• /
• pp.23-29
• /
• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of promethazine in human serum was developed, validated, and applied to the pharmacokinetic study of promethazine. Promethazine and internal standard, chlorpromazine, were extracted from human serum by liquid-liquid extraction with n-hexane containing 0.8% isopropanol and analyzed on a Capcell Pak CN column with the mobile phase of acetonitrile-0.2 M potassium dihydrogen phosphate (42:58, v/v, adjusted to pH 6.0 with 1 M NaOH). Detection wavelength of 251 nm and flow rate of 0.9 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed promethazine concentration (10 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 1-40 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 1 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 96.15 to 105.40% for promethazine with overall precision (% C.V.) being 6.70-11.22%. The relative mean recovery of promethazine for human serum was 63.54%. Stability (freeze-thaw and short-term) studies showed that promethazine was stable during storage, or during the assay procedure in human serum. However, the storage at $-80^{\circ}C$ for 4 weeks showed that promethazine was not stable. Extracted serum sample and stock solution were not allowed to stand at ambient temperature for 12 hr prior to injection. The peak area and retention time of promethazine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of promethazine in human serum samples for the pharmacokinetic studies of orally administered Himazin tablet (25 mg as promethazine hydrochloride) at three different laboratories, demonstrating the suitability of the method.

• Clinical and Experimental Pediatrics
• /
• v.58 no.9
• /
• pp.347-353
• /
• 2015

Purpose: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). Methods: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. Results: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). Conclusion: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.

• Biomolecules & Therapeutics
• /
• v.6 no.3
• /
• pp.289-295
• /
• 1998

The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca $l_{R}$ tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi $l_{R}$ tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4$\pm$ 10.24% (mean$\pm$ 5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-$_{8 hr}$) (22.8$\pm$5.90 vs 22.2$\pm$6.10 ng . hr/ml), maximum plasma concentration ( $C_{max}$) (10.0$\pm$2.85 vs 9.3$\pm$3.28 ng/ml) and time to reach maximum plasma concentration ( $T_{max}$) (1.2$\pm$0.31 vs 1.3 $\pm$0.47 hr). The differences of mean AU $Co_{8hr}$ $C_{max}$, and $T_{max}$ between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-$\beta$) and treaeent difference (7) for AU $Co_{8hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.

• Journal of Veterinary Clinics
• /
• v.32 no.2
• /
• pp.215-217
• /
• 2015

There was no study on the prevalence of doping control of racehorses in Korea. The purpose of this study was to determine prohibited substances in horse races of a drugs testing program. Blood samples were taken from those 298,543 starters prior to racing and the that finished top 3 runners of each race and horses designated by the stewards shall be taken for collection of 91,482 urine samples for the purpose of post-race doping test in Seoul, Busan and Jeju Race Park between 2002 and 2013. Detection and measurement of prohibited substances were carried out by ELISA, GC/MS and LC/MS using standard methods at the Doping Control Center, Korea Racing Authority. Total 0.0030% of pre-races and total 0.0186% of post-races tested positive for prohibited substances. In pre- and post-race, caffeine and ketoprofen were the most detected prohibited substance respectively. We thought that characteristics of pharmacokinetics and pharmacodynamics of drugs resulted in different between plasma and urine. These substances have also been detected with other prohibited drugs suggesting that unintentional feeding or bedding may be the reason and groomers' confusion of candidate horses based by the stewards' research.

• Journal of Society of Preventive Korean Medicine
• /
• v.21 no.2
• /
• pp.1-13
• /
• 2017

Objectives : This paper serves to explore current trends of systems biology in Traditional Chinese Medicine (TCM) and examine how it may influence the Traditional Korean medicine. Methods : Literature review method was collectively used to classify Introduction to systems biology, diagnosis and syndrome classification of systems biology in TCM perspective, physiotherapy including acupuncture, herbs and formula functions, TCM systems biology, and directions of academic development. Results : The term 'Systems biology' is coined as a combination of systems science and biology. It is a field of study that tries to understand living organism by establishing a theory based on an ideal model that analyzes and predicts the desired output with understanding of interrelationships and dynamics between variables. Systems biology has an integrated and multi-dimensional nature that observes the interaction among the elements constructing the network. The current state of systems biology in TCM is categorized into 4 parts: diagnosis and syndrome, physical therapy, herbs and formulas and academic development of TCM systems biology and its technology. Diagnosis and syndrome field is focusing on developing TCM into personalized medicine by clarifying Kidney yin deficiency patterns and metabolic differences among five patterns of diabetes and analyzing plasma metabolism and biomarkers of coronary heart disease patients. In the field of physical therapy such as acupuncture and moxibustion, researchers discovered the effect of stimulating acupoint ST40 on gene expression and the effects of acupuncture on treating functional dyspepsia and acute ischemic stroke. Herbs and formulas were analyzed with TCM network pharmacology. The therapeutic mechanisms of Si Wu Tang and its series formulas are explained by identifying potential active substances, targets and mechanism of action, including metabolic pathways of amino acid and fatty acid. For the academic development of TCM systems biology and its technology, it is necessary to integrate massive database, integrate pharmacokinetics and pharmacodynamics, as well as systems biology. It is also essential to establish a platform to maximize herbal treatment through accumulation of research data and diseases-specific, or drug-specific network combined with clinical experiences, and identify functions and roles of molecules in herbs and conduct animal-based studies within TCM frame. So far, few literature reviews exist for systems biology in traditional Korean medicine and they merely re-examine known efficacies of simple substances, herbs and formulas. For the future, it is necessary to identify specific mechanisms of working agents and targets to maximize the effects of traditional medicine modalities. Conclusions : Systems biology is widely accepted and studied in TCM and already advanced into a field known as 'TCM systems biology', which calls for the study of incorporating TCM and systems biology. It is time for traditional Korean medicine to acknowledge the importance of systems biology and present scientific basis of traditional medicine and establish the principles of diagnosis, prevention and treatment of diseases. By doing so, traditional Korean medicine would be innovated and further developed into a personalized medicine.

• Toxicological Research
• /
• v.6 no.2
• /
• pp.205-213
• /
• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

• Korean Journal of Veterinary Research
• /
• v.57 no.4
• /
• pp.215-222
• /
• 2017

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350-400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.

• Journal of Pharmaceutical Investigation
• /
• v.22 no.3
• /
• pp.229-235
• /
• 1992

The bioequivalence of two commercial choline magnesium trisalicylate (CMT) tablets was evaluated in 10 normal male subjects (age 21-27 yr, mean 23 yr) following single oral administrations of two products. Test product was $Trimax^{\circledR}$ tablet (Hyundai Pharm. Ind. Co., Ltd., Korea) and reference product was $Trilisate^{\circledR}$ tablet (Purdue Frederick, U.S.A.). Both products contained 500 mg salicylate. In the study, ten volunteers were administered one tablet of $Trimax^{\circledR}$ or $Trilisate^{\circledR}$ with randomized two period cross-over study. The pharmacokinetic parameters of two products were statistically compared using Student's t-test and ANOVA. When Student's t-test was applied, mean area under the curves (AUC) of $Trilisate^{\circledR}$ and $Trimax^{\circledR}$ were $388.88{\pm}74.99\; {\mu}g{\cdot}hr/ml$ and $390.63{\pm}63.02\;{\mu}g{\cdot}hr/ml$ hrlm!, respectively, which were not significantly different (p>0.05). The mean peak concentrations $(C_{max})$ and mean times to peak $(T_{max})$ of $Trilisate^{\circledR}$ and $Trimax^{\circledR}$ were $71.1{\pm}12.2$ and $72.9{\pm}10.7\;{\mu}g/ml$, and $72{\pm}33$ and $57{\pm}36min$, respectively, which were not significantly different (p>0.05). The mean terminal phase half-lives $(t_{l/2ter})$ of the two products were $2.57{\pm}0.47$ and $2.43{\pm}0.40$ hr, and also they were not significantly different (p>0.05). When ANOVA was applied, the parameters of the two products were not also significantly different each other. Based on the above results, it has been concluded that the bioavailability of $Trimax^{\circledR}$ tablet was not significantly different from that of $Trilisate^{\circledR}$ tablet.