• YAKHAK HOEJI
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• v.34 no.4
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• pp.238-243
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• 1990

Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

• Analytical Science and Technology
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• v.25 no.4
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• pp.250-256
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• 2012

Two marker compounds of Achyranthis Radix, ecdysterone and inokosterone, were analyzed by HPLC on an ODS column ($250{\times}4.6$ mm, 5 ${\mu}m$) with a mobile phase of 15% acetonitrile containing 0.08% formic acid at a flow rate of 1.0 mL/min and a detection wavelength of UV 254 nm. The method was validated by ICH guideline and applied to the monitoring of marker compounds in 93 samples of Achyranthis Radix collected at various areas in Korea and China. The new content criteria of ecdysterone and inokosterone, established using linear regression method were 0.033% and 0.020%, respectively. When the new content criteria were applied to the quality control test of commercial Achyranthis Radix, 95.4% of total samples including 100% of Korean and 92.6% of Chinese samples were passed the test. Application of new content criteria could protect the Korean products and decrease the distribution of Chinese products with lower quality.

• Journal of Veterinary Clinics
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• v.23 no.2
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• pp.87-90
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• 2006

The aim of the present study was to investigate the disposition pharmacokinetics of roxithromycin in broilers. Roxithromycin was administered at a single dose of 20 mg/kg body weight by intravenous (i.v.) routes. Plasma concentrations of roxithromycin were determined by liquid chromatography/mass spectrometry. After a single i.v. dose plasma concentrations were best fitted to a two-compartment open model. The values of the pharmacokinetic parameters after i.v. administration were: elimination half-life = $5.83{\pm}1.79h$, mean residence time = $6.33{\pm}0.32h$, total body clearance = $0.55{\pm}0.15L/h/kg$, and volume of distribution at steady state = $3.47{\pm}0.84L/kg$. The pharmacokinetic interpretation of roxithromycin after i.v. administration revealed that the drug was well distributed throughout the body in broilers and slowly eliminated. More studies for the application of roxithromycin against poultry disease are needed to establish a suitable pharmaceutical formulation, propose optimum dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.101-107
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• 2010

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

• Journal of Gastric Cancer
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• v.15 no.4
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• pp.223-230
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• 2015

Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

• Sleep Medicine and Psychophysiology
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• v.3 no.1
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• pp.47-55
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• 1996

Narcolepsy is characterized by sleep attack with excessive daytime sleepiness(EDS), cataplexy, sleep paralysis, and hypnagogic hallucination. Paradoxically, narcoleptics tend to complain of frequent arousals and shallow sleep during the night time despite their excessive sleepiness. However, nocturnal sleep fragmentation in narcoleptics is relatively ignored in treatment strategies, compared with sleep attack/EDS and cataplexy. In our paper, we attempted to investigate further on the poor nocturnal sleep in narcoleptics and to discuss possible treatment interventions. Out of consecutively seen patients at Seoul National University Sleep Disorders Clinic and Division of Sleep Studies, we recruited 57 patients, clinically assessed as having sleep attack and/or EDS. Nocturnal polysomnography and multiple sleep latency test(MSLT) were done in each of the subjects. We selected 19 subjects finally diagnosed as narcolepsy(mean age $26.0{\pm}18.3$ years, 16 men and 3 women) for this study, depending on the nocturnal polysomnographic and MSLT findings as well as clinical history and symptomatology. Any subject co-morbid with other hypersomnic sleep disorders such as sleep apnea or periodic limb movements during sleep was excluded. Sleep staging was done using Rechtschaffen and Kales criteria. Sleep parameters were calculated using PSDENT program(Stanford Sleep Clinic, version 1.2) and were compared with the age-matched normal values provided in the program. In narcoleptics, compared with the normal controls, total wake time was found to be significantly increased with significantly decreased sleep efficiency(p<.01, p<.05, respectively), despite no difference of sleep period time and total sleep time between the two groups. Stage 2 sleep%(p<.05), slow wave sleep%(p<.05), and REM sleep%(p<.01) were found to be significantly decreased in narcoleptics compared with normal controls, accompanied by the significant increase of stage 1 sleep%(p<.01). Age showed negative correlation with slow wave sleep%(p<.05). The findings in the present study indicate significant fragmentation of nocturnal sleep in narcoleptics. Reduction of REM sleep% and the total number of REM sleep periods suggests the disturbance of nocturnal REM sleep distribution in narcoleptics. No significant correlations between nocturnal polysomnographic and MSLT variables in narcoleptics suggest that nocturnal sleep disturbance in narcoleptics may be dealt with, in itself, in diagnosing and managing narcolepsy. With the objective demonstration of qualitative and quantitative characteristics of nocturnal and daytime sleep in narcoleptics, we suggest that more attention be paid to the nocturnal sleep fragmentation in narcoleptics and that appropriate treatment interventions such as active drug therapy and/or circadian rhythm-oriented sleep hygiene education be applied as needed.

• Journal of The Korean Dental Society of Anesthesiology
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• v.4 no.2 s.7
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• pp.84-89
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• 2004

Background: Many studies on efficacy of preemptive analgesia have been processed in different ways. But the value of preemptive analgesia is still controversial. The goal of this study was to compare analgesic effect of an NSAID according to three different administration times for oral surgical pain. Patients and Methods: Using a randomized, parallel-group, single-center, and active-controlled test design, this study was conducted to healthy 80 patients undergoing a surgical removal of an impacted mandibular third molar requiring bone removal. The oral NSAID was first administered 1 hour preoperatively, or 1 hour postoperatively, or no scheduled administration in pre or postsurgery. Whenever patients felt at least moderate pain (score ${\ge}$ 5 on a 10-point scale) after surgery, they were instructed to take the same drug. Pain intensities and times to the first and second onset of postoperative pain from end of surgery were assessed for 24 hours. Results: Of the enrolled eighty subjects in this study, 25 patients were assigned to preemptive, 26 to post-treatment and 29 to no treatment group. The demographic distribution and duration of surgery in the three groups were statistically similar. The mean time to first onset of postoperative pain was significantly prolonged in post-treatment group (277.2 minutes, p < 0.05) compared to preemptive (158.4 minutes) and no treatment group (196.5 minutes). The mean time to second onset of postoperative pain was not significantly different among the three groups. No significant statistical difference was found among the mean pain intensities at the first and second onset of postoperative pain in the three groups. Conclusions: In this small selected group of subjects and limited study design, the analgesic effects of NSAID administered preoperatively were no longer effective for postoperative pain. The results in this population imply that scheduled postoperative analgesics before pain development are adequate for postoperative analgesia without preoperative administration.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.5
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• pp.677-684
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• 1998

The distribution and elimination of oxolinic acid (OA) following oral (80mg/kg body weight) and bath (20 mg/$\ell$) treatment were examined in the organs and plasma of Nile tilapia (Oreochromis niloticus) on different temperatures and physiological conditions using a bioassay method. On the analysis of temperature effect, both absorption and elimination of OA after oral administration were delayed in the group at $15^{\circ}C$. but significant difference of the peak concentrations in the tissues of the groups at $15^{\circ}C$ and $25^{\circ}C$ was not revealed. However, the changes of maximam concentration, absorption and elimination rates in the tissues of fish following bath treatment depending on different temperatures were more significantly different from the results of the studies with oral administration. The pharmacokinetics of OA in the tissues of diseased fish, the main target of drug treatment, also appeared to be distinguishable from those of healthy fish.

• Journal of Biomedical Engineering Research
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• v.25 no.6
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• pp.581-587
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• 2004

Conventional power spectrum methods based on FFT, AR method are not appropriate for analyzing biomedical signals whose spectral characteristics change rapidly. On the other hand, time-frequency analysis has more desirable characteristics of a time-varying spectrum. In this study, we investigated the spectral components of heart rate variability(HRV) in time-frequency domain using time frequency analysis methods. In the various time-frequency kernels functions, we studied the suitable kernels for the analysis of HRV using synthetic HRV signals. First, we evaluated the time/frequency resolution and cross term reduction of various kernel functions. Then, from the instantaneous frequency, obtained from time-frequency distribution, the method extracting frequency components of HRV was proposed. Subjects were 17 healthy young men. A coin-stacking task was used to induce mental stress. For each subjects, the experiment time was 3 minutes. Electrocardiogram, measured during the experiment, was analyzed after converted to HRV signal. In the results, emotional stress of subjects produced an increase in sympathetic activity. Sympathetic activation was responsible for the significant increase in the LF/HF ratio. Subjects were divided into two groups with task ability. Subjects who have higher mental stress have lack of task ability.

• The Korean Journal of Nuclear Medicine
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• v.21 no.2
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• pp.133-141
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• 1987

To evaluate the values of the thyroid autoantibody measured by radioimmunoassay (RIA) and compare it with hemagglutination method (HA) in the normal and the thyroid disease, data were obtained from total 618 persons; 236 healthy persons, 217 patients with Graves' disease (including 113 patients with undertreated Graves' disease), 100 Hashimoto's disease, 31 thyroid nodule, and 34 simple goiter. RSR kit made in England was used and could be detected to at least 3 U/ml. The positive rates of normal group were antimicrosomal antibody (AMA) 31.8%, antithyroglobulin antibody (ATA) 44.5% by RIA and there was no considerable change in sex and age distribution. In Graves' disease, the positive rates of AMA and ATA were 90.4, 76.9% by RIA, 85, 39% by HA. In Hashimoto's disease, 94,91 % by RIA, and 87,48% by HA, respectively. The autoantibody titer by RIA in thyroid autoimmune disease as well as in normal group was more senisitive than that by HA, especially in ATA. There were linear relationships between the titer of RIA and that of HA in AMA of Graves' disease and AMA and ATA of Hashimoto's disease. There was no relationship among thyroid autoantibody, free $T_4$ index, TBII, and TSH. The titers of AMA and ATA were found to decrease in patients with Graves' disease during the course of antithyroid drug therapy. Of the 236 normal subjects, thirty-seven (15.7%) had concentrations of above 7.5 U/ml in AMA, forty. four (18.6%) above 9 U/ml in ATA. These values were considered as the upper limit for the normal range. In Graves' disease, 82.7, 53.8% were above 7.5, 9 U/ml, respectively; In Hashimoto's disease, 82, 79% were positive. We conclude that RIA was more sensitve than HA in measuring the thyoird autoantibody, but we will study further more for determining the normal range and its interpretation.