• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.265-270
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• 1995

The pharmacokinetics of norfloxacin (100 mg/kg, oral) in renal failure rabbits was studied. Renal failure rabbits were induced by the i.v. injection of folate (50,100 and 150 mg/kg). These produced significant increases of serum creatinine concentration $(S_{cr})$ and blood urea nitrogen (BUN). Plasma concentration and AUC of norfloxacin significantly increased. Elimination rate constant $(K_{el})$ of norfloxacin significantly decreased, and half-life $(t_{1/2})$ of norfloxacin significantly increased. Correlation between serum creatinine concentration $(S_{cr})$ and half-life $(t_{1/2})$ of norfloxacin, and correlation between BUN and AUC of norfloxacin have linear relationship respectively. These results suggest that adjustment or the dosage regimen of norfloxacin is desirable, and serum creatinine concentration $(S_{cr})$ as well as BUN can be used an index for adjusting the dosage regimen of norfloxacin in renal failure.

• BMB Reports
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• v.46 no.12
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• pp.606-610
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• 2013

Glucagon like peptide-1 (GLP-1) regulates glucose mediated-insulin secretion, nutrient accumulation, and ${\beta}$-cell growth. Despite the potential therapeutic usage for type 2 diabetes (T2D), GLP-1 has a short half-life in vivo ($t_{1/2}$ <2 min). In an attempt to prolong half-life, GLP-1 fusion proteins were genetically engineered: GLP-1 human serum albumin fusion (GLP-1/HSA), AGLP-1/HSA which has an additional alanine at the N-terminus of GLP-1, and AGLP-1-L/HSA, in which a peptide linker is inserted between AGLP-1 and HSA. Recombinant fusion proteins secreted from the Chinese Hamster Ovary-K1 (CHO-K1) cell line were purified with high purity (>96%). AGLP-1 fusion protein was resistant against the dipeptidyl peptidase-IV (DPP-IV). The fusion proteins activated cAMP-mediated signaling in rat insulinoma INS-1 cells. Furthermore, a C57BL/6N mice pharmacodynamics study exhibited that AGLP-1-L/HSA effectively reduced blood glucose level compared to AGLP-1/HSA.

• Korean Journal of Clinical Pharmacy
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• v.8 no.1
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• pp.23-28
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• 1998

The pharmacokinetics of atenolol (25 mg/kg, i.v.) in the folate-induced renal failure rabbits was studied. Renal failure was induced by the i.v. injection of folate (50, 100, and 200 mg/kg). At folate dose of 100 and 200 mg/kg, the serum creatinine concentration (Scr) and blood urea nitrogen (BUN) increased significantly compared with control rabbits. Plasma concentrations and AUC of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The elimination rate constant $(K_{el})$ and total body clearance $(CL_t)$ of atenolol decreased significantly, and half-life ($t_{1/2}$) and mean residence time (MRT) of atenolol increased significantly at folate dose of 100 and 200 mg/kg. The serum creatinine concentration $(S_{cr})$ correlated well (p<0.05) with half-life $(t_{1/2})$ and elimination rate constant $(K_{el})$ of atenolol, as well as BUN with AUC and total body clearance $(CL_t)$ of atenolol.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.259-264
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• 2004

The purpose of the present study was to investigate the pharmacokinetics of PEG-hemoglobin SB 1, a modified bovine hemoglobin with polyethylene glycol, after its single and multiple administration in beagle dogs. For this purpose, the analytical method of free hemoglobin in the plasma was developed and validated. Excellent linearity ($r^2$=0.999) was observed in the calibration curve data, with the limit of quantification of 0.005 g/dL. The precision and the deviation of the theoretical values for accuracy were always within $\pm$15％ in both the between-and the within-day results. The method was tested by measuring the plasma concentrations following intravenous administration to beagle dogs and was shown to be suitable for pharmacokinetic studies. In a single dose study, the plasma half-life (t$_{1}$2/) increased and the total body clearance (Cl$_{t}$) decreased with the dose (i.e., 0.017 to 0.75 gHb/kg as PEG-hemoglobin SB1) in both sexes. The volume of distribution at steady-state (Vd$_{ss}$ ) showed no difference with the dose. In contrast, the values of t$_{1}$2/, CL$_{t}$ and the area under the plasma concentration-time curve (AUC) after the multiple dose were significantly different from those of the single dose administration. The values of t$_{1}$2/ in the multiple administration were about two times higher-than that of the single dose. As a result, t$_{1}$2/ of hemoglobin after the administration of PEG-hemoglobin SB1 was about 15-30 h, indicating the PEG modification of the hemoglobin lead to a prolongation of plasma concentration of the protein. Therefore, these observations suggested that the PEG modification of hemoglobin is potentially applicable in the hemoglobin-based therapeutics.tics.

• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

• Korean Journal of Veterinary Research
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• v.42 no.1
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• pp.45-54
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• 2002

The study was carried out to characterize the pharmacokinetics after intravenous (iv, 20 mg/kg) and oral (p.o. 100 mg/kg) administration as oxytetracycline (OTC) and tiamulin (TIA) mixture in swine and to determine interaction between OTC and TIA against various pig pathogenic bacteria. The antibacterial effects of OTC in combination with TIA in vitro showed synergistic effect against Salmonella typhimurium 1925, Pasteurella multocida Type A, P. multocida Type D, Krebsiella Pneumoniae 2001, K. Pneumoniae 1560, K. Pneumoniae 2208, Haemophillus pleuropneumonia S 2, and H. pleuropneumonia S 5, but against additive effect E. coli K88ab and S. choleraesuis on the basis of fractional inhibitory concentration (FIC) index. On the while, after i.v. and p.o. administration of OTC and TIA mixture, each OTC and TIA concentrations in plasma were fitted to an open two-compartment model. After i.v. administration of OTC-TIA mixture, the mean distribution half-life ($T_{1/2{\alpha}}$) of OTC and TIA in plasma showed 0.29 h and 0.17 h, and the mean elimination half-life ($T_{1/2{\beta}}$) of those was 4.36 h and 6.64 h, respectively. The mean volume of distribution at steady state ($Vd_{ss}$) of OTC and TIA was $0.85{\ell}/kg$ and $2.44{\ell}/kg$, respectively. After oral administration of OTC and TIA mixture, the mean maximal absorption concentrations ($C_{max}$) of OTC and TIA were $0.60{\mu}g/m{\ell}$ at 1.07 h ($T_{max}$) and $1.68{\mu}g/m{\ell}$ at 1.85 h ($T_{max}$), respectively. The mean elimination half-life ($T_{1/2{\beta}}$) of those showed 6.84 h and 6.36 h. In conclusion, we could suggest in this study that the combination of OTC and TIA may be recommended for the antibacterial therapy against polymicrobial infections, and both OTC and TIA showed large distribution to tissues and high $C_{max}$ after p.o. administration.

• The Journal of Internal Korean Medicine
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• v.39 no.4
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• pp.570-591
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• 2018

Objective: This study was designed to investigate the correlation between gastric emptying measurement by ultrasonography and the findings of various questionnaires of functional dyspepsia (FD) or in Korean medicine to explore the possibility of quantification of questionnaires. Methods: Eighty-eight patients (44 patients with FD and 44 healthy controls) were recruited from October 2016 to November 2017. Gastric emptying half-time (T1/2) was measured by ultrasonography at fasting, and at 0, 15, 30, 45, 60, 90, and 120 min after meals (apple juice, 500 ml, 224 kcal). The average half-time (average T1/2) was calculated by averaging all measured half-times. A visual analogue scale (VAS), food retention questionnaire (FRQ), damum questionnaire (DQ), cold and heat questionnaire (CHQ), deficiency and excess questionnaire (DEQ), spleen-qi deficiency questionnaire (SQDQ), Nepean dyspepsia index-Korean version (NDI-K), and quality of life of NDI (NDI-QoL) were filled out by all participants. Correlation between the average T1/2 and questionnaires were analyzed for 79 patients (37 patients with FD and 42 healthy controls) after excluding missing and erroneous data. Results: The FRQ, DEQ, SQDQ, NDI-K, and NDI-QoL scores, especially for some gastrointestinal symptoms and general weakness-related symptoms, showed statistically significant correlations with average T1/2. Conclusions: Our results suggest that gastric emptying measurement by ultrasonography may be a quantitative substitute method for some Korean medical questionnaires or for some dyspepsia-related and deficiency-related items among them. However, further studies using various measurements of gastric emptying will be needed.

• Journal of Radiation Protection and Research
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• v.46 no.4
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• pp.178-183
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• 2021

Background: This study was carried out to provide environmental transfer parameter values to estimate activity concentrations of these radionuclides in agricultural crops when direct contamination occurred. Materials and Methods: Mass interception fractions (F_Bs) and weathering half-lives (T_ws) of ¹³¹I and radiocesium were calculated using openly available monitoring data obtained after the Fukushima Daiichi Nuclear Power Plant accident. F_B is the ratio between the initial radioactivity concentration of a radionuclide retained by the edible part of the plant (Bq·kg^-1 fresh weight [FW]) and the amount of deposited radionuclide in that area (Bq·m^-2). T_w values can be calculated using activity concentrations of crops decreased with time after the initial contamination. Results and Discussion: Calculated F_B and T_w values for ¹³¹I and radiocesium were mostly obtained for leafy vegetables. The analytical results showed that there was no difference of F_Bs between ¹³¹I and radiocesium by t-test; geometric mean values for leafy vegetables cultivated under outdoor conditions were 0.058 and 0.12 m²·kg^-1 FW, respectively. Geometric mean T_w value of ¹³¹I in leafy vegetables grown under outdoor conditions was 8.6 days, and that of radiocesium was 6.6 days; there was no significant difference between T_w values of these radionuclides by Wilcoxon rank sum test. Conclusion: There was no difference between ¹³¹I and radiocesium for F_Bs and T_ws. By using these factors, we would be able to carry out a rough estimation of the activity concentrations of ¹³¹I and radiocesium in the edible part of leafy crops when a nuclear accident occurred.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.444-459
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• 2003

Ethosuximide is an oral anticonvulsantic agent used in the first choice anti-absence seizure drug. The purpose of this study was to assess the pharmacokinetic profile of the ethosuximide in healthy Korean volunteers and to develop the efficient assay method of ethosuximide in human plasma. The pharmacokinetics of ethosuximide administered orally was evaluated after a dose of 500 mg. Ethosuximide was assayed from plasma by a specific HPLC method reading absorbance at 195 nm. AUC was 1222$\pm$160 $\mu\textrm{g}$/$m\ell$$.$hr, $C_{max}$ 14.2l$\pm$1.74 $\mu\textrm{g}$/$m\ell$, $T_{max}$ 1.06$\pm$0.62 hr and half-life 77.83$\pm$12.46 hr. The half-life in Korean was longer than, in Caucasian (53∼56 hr).).).

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.253-263
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• 1997

To investigate the interaction of omeprazole (OMP) and meglumine (MEG), a complex was prepared by freeze-drying method in ammoniacal aqueous medium at room temperature and subjected to IR, DSC, and 1H NMR analysis. In addition, the stability of the complex was tested by accelerated stability analysis, and the dissolution rate of both powder and enteric coated was determined pellet by paddle method. The results are as follows; i) IR, DSC, and $^{1}H$ NMR studies indicate the formation of inclusion complex between OMP and MEG probably by electrostatic forces as $[OMP]\;[MEGH]^+$ form in a stoichiometric ratio (1:1) of OMP : MEG. ii) The dissolution rate of enteric coated OMP-MEG complex pellet in simulated enteric fluid was 90.6% in 10 minutes, which may satisfy the requirement for the regulation of dissolution. iii) OMP-MEG complex were decomposed according to pseudo 1st order kinetics: while the decomposition of OMP showed a rate constant $(k_{25^{\circ}C})$ of $5.13{\times}10^{-4}{\cdot}\;day^{-1}$, a half-life$(t_{1/2})$ of 1,350 days, a shelf-life$(T_{90%})$ 205 days and an activation energy of 23.53 kcal/mole. OMP-MEG complex inhibited a rate $(k_{25})$ of $2.92{\times}10^{-4}{\cdot}\;day^{-1}$, a half-life$(t_{1/2})$ of 2,373 days, a shelf-life $(T_{90%})$ of 306 days and an activation energy of 20.18 kcal/mole. iv) OMP was stabilized markedly by the formation of OMP-MEG complex between OMP and MEG, and the humidity increased the stability of OMP-MEG complex by decreasing the decomposition rate$(k_{50^{\circ}C})$ from $1.27{\times}10^{-2}{\cdot}\;day^{-1}$ at 31% R.H. to $2.54{\times}10^{-2}{\cdot}\;day^{-1}$ at 90% R.H.