• Journal of Life Science
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• v.9 no.3
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• pp.241-247
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• 1999

Antibiotics have been routinely used to control the disease of farm-raised animals in the aquaculture facilities without any criterion based on a pharmacokinetic study. This lack of information on the effective usage of antibiotics would have brought the farmers to use excessive and/or less dosages, causing the advent of drug-resistant bacteria as well as economic loss and possible contamination of the local farming area. Until recently, few studies on a detailed manual for the antibiotic usage including chemotherapy procedure, dosage, and treatment schedule of the aquatic antibiotics have been conducted throughout the world. To the worse, there is no available criterion for optimal usage of aquatic antibiotics to control diseases in aquatic farms in this country because every country has its own aquacultural system. Therefore, based on the previous studies on the usage of the various antibiotics, our studies are to focus on the development of optimal method for the detection of various antibiotics on the fate of antibiotics applied to the fish, including absorption, circulation, and secretion physiology. Pharmacokinetic study were to sep up the optimal detective condition against residual antibiotics of fish by HPLC. The grinding pefloxacin for 15 min is most effective in dissolution test and pharmacokinetic parameters. Pharmacokinetic parameters were satisfactory for 15 min-grinding products and they can be explained as one-compartment model.

• Korean Journal of Clinical Pharmacy
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• v.26 no.2
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• pp.150-162
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• 2016

Objective: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. Methods: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. Results: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. Conclusion: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.195-202
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• 1997

The purpose of this study was to determine pharmacokinetic parameters of vancomycin using two point calculation(TPC) and Bayesian methods in 16 Korean normal volunteers and 15 g astric cancer patients. Nonparametric expected maximum(NPEM) algorithm for calculation of population pharmacokinetic parameter was used, and these parameters were applied for clinical pharmacokinetic parameters by Bayesian analysis. Vancomycin was administered 1.0g every 12 hrs for 3 days by IV infusion over 60 minutes. The volume of distribution(Vd), elimination rate constant(Kel) and total body clearance(CLt) of vancomycin in normal volunteers using TPC method were $0.34{\pm}0.06 L/kg,\; 0.19{\pm}0.01 hr^{-1}$ and $4.08 {\pm} 0.93 L/hr$, respectively, The Vd, Kel and CLt of vancomycin in gastric cancer patients using TPC method were $0.46 {\pm} 0.06 L/kg, 0.17{\pm}0.02 hr^{-1}$ and $4.84 {\pm} 0.57 L/hr$ respectively. There were significant differences(p<0.05) in Vd. Kel and CLt between normal volunteers and gastric cancer patients. Polpulation pharmacokinetic parameter, the slope(KS) of the relationship beetween Kel versus creatinine Clearance, and the Vd were $0.00157{\pm}0.00029(hr{\cdot}mL/min/1.73m^2)^{-1},\; 0.631 {\pm} 0.0036 L/kg$ in gastric cancer patients using NPEM algorithm respectively. The Vd and Kel were $0.63{\pm}0.005 L/kg, 0.15 {\pm}0.027 hr^{-1}$ for gastric cancer patients using Bayesian method. There were significant differences(p<0.05) in vancomycin pharmacokinetics between Bayesian and TPC methods. It is considered that the population parameter in the patient population is necessary for effective Bayesian method in clinical pharmacy practise.

• The Korean Journal of Applied Statistics
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• v.24 no.4
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• pp.623-631
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• 2011

A major goal of time-course microarray data analysis is the detection of groups of genes that manifest similar expression patterns over time. The corresponding numerous cluster algorithms for clustering time-course microarray data have been developed. In this study, we proposed a clustering method based on the primary pharmacokinetic parameters in the pharmacokinetics study for assessment of pharmaceutical equivalents between two drug products. A real data and a simulation data was used to demonstrate the usefulness of the proposed method.

• Journal of Veterinary Clinics
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• v.24 no.1
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• pp.5-9
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• 2007

The purpose of this study was to examine the allometric analysis of roxithromycin using pharmacokinetic data. The pharmacokinetic parameters used were $half-life(t_{1/2})$, mean residence time (MRT), clearance (Cl) and volume of distribution at steady state $(V_{ss})$. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula $Y=aW^b$, where 'Y' is $t_{1/2}$, MRT, Cl, or $V_{ss}$, W the body weight and 'a' is an allometric coefficient (intercept) that is constant for a given drug. The exponential term, 'b', is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. As results of the allometric analyses, the logarithms of $t_{1/2}$, MRT, Cl, and $V_{ss}$ were linearly related to the logarithms of body weight. Results of the current analyses could provide information on appropriate doses of roxithromycin for all species.

• YAKHAK HOEJI
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• v.39 no.6
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• pp.636-644
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• 1995

Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.

• Korean Journal of Clinical Pharmacy
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• v.7 no.2
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• pp.51-63
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• 1997

The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.

• Biomolecules & Therapeutics
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• v.11 no.3
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• pp.178-182
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• 2003

The clinical use of once daily aminoglycoside (ODA) dosing has been increased because of the potential therapeutic advantages of this dosing regimen. To evaluate the optimal sampling times of ODA dosing method in a clinical setting, the study was prospectively conducted in a total of 28 patients with UTI. All of the patients were intravenously administered gentamicin at a dose of 7 mg/kg over 60 minutes and randomly divided into two groups. Blood was collected at 0, 2, and 6 hours in Group A and at 1, 2, and 6 hours in Group B after the end of 1-hour infusion. The pharmacokinetic parameters (Ke, Vd and Cmax) obtained using the 0, 6 hour levels and 2, 6 hour levels in Group A were statistically different while those of 1, 6 hour levels and 2, 6 hour levels in Group B were similar. This finding indicated that the distributional phase of ODA is completed within 1 hour following the end of the I-hour infusion. If we are allowed to collect only two blood samples in ODA considering patients comfort and the analytical cost of drug, the first one should be drawn after 1 hour following the end of infusion to obtain adequate pharmacokinetic information.

• Biomaterials and Biomechanics in Bioengineering
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• v.2 no.3
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• pp.127-141
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• 2015

Silver-based systems activated by low intensity direct current continue to be investigated as an alternative antimicrobial for infection prophylaxis and treatment. However there has been limited research on the quantitative characterization of the antimicrobial efficacy of such systems. The objective of this study was to develop a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model providing the quantitative relationship between the critical system parameters and the degree of antimicrobial efficacy. First, time-kill curves were experimentally established for a strain of Staphylococcus aureus in a nutrientrich fluid environment over 48 hours. Based on these curves, a modified PK/PD model was developed with two components: a growing silver-susceptible bacterial population and a depreciating bactericidal process. The test of goodness-of-fit showed that the model was robust and had good predictability ($R^2>0.7$). The model demonstrated that the current intensity was positively correlated to the initial killing rate and the bactericidal fatigue rate of the system while the anode surface area was negatively correlated to the fatigue rate. The model also allowed the determination of the effective range of these two parameters within which the system has significant antimicrobial efficacy. In conclusion, the modified PK/PD model successfully described bacterial growth and killing kinetics when the bacteria were exposed to the electrically activated silver-titanium implant system. This modeling approach as well as the model itself can also potentially contribute to the development of optimal design strategies for other similar antimicrobial systems.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.296-302
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• 1998

The bioequivalence of two cyclosporin A products was evaluated in 26 normal male volunteers (age 25 ~33 yr, body weight 56~84 kg) following single oral administration. Test product was a hard capsule containing the granule of cyclosporin A (Chong Kun Dang Corp., Korea) and reference product, Sandimmun", was a soft capsule containing surfactant, oil, alcohol and cyclosporin A (Sandoz, Swiss). Both products contain 100 mg of cyclosporin A. Four capsules of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). Average drug concentrations at each sampling time and pharmacokinetic parameters were not significantly different between two products (p>0.05); the area under the concentration-time curve to last sampling time (24 hr) (AU $Co_{24}$) (5034.8$\pm$ 1760.6 vs 4635.4$\pm$ 1158.9 ng . h/ml), maximum plasma concentration ( $C_{max}$) (1002.7$\pm$353.1 vs 980. 4$\pm$ 171.7 ng/71), and mean residence time (MRT) (6.16$\pm$0.81 vs 5.64$\pm$0.50 h). The differences of mean AUC 7-,4,7~, T_ and MRT between the two products (7.93,2.22,16 and 8.39%, respectively) were less than 20% given as a guideline. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24}$, $C_{max}$ and MRT were more than 0.8 and less than 0.2, respectively. Although $T_{max}$ of the two products was significantly different each other (p<0.05), $T_{max}$ might be an insignificant parameter because cyclosporin A generally requires long-term administration. From these results, the two products are bioequivalent.alent.t.