• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.84-87
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• 2003

The purposes of this study were to evaluate the population pharmacokinetics of levosulpiride and terbinafine according to several pharmacokinetic models and to investigate the influence of characteristics of subjects such as age, body weight, height and serum creatinine concentration on the pharmacokinetic parameters of levosulpiride and terbinafine, respectively. (omitted)

• 한국임상약학회지
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• 제27권2호
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• pp.63-68
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• 2017

Neonates have large inter-individual variability in pharmacokinetic parameters of many drugs due to developmental differences. The aim of this study was to investigate the factors affecting the pharmacokinetic parameters of drugs, which are commonly used in critically ill neonates. Factors that reflect physiologic maturation such as gestational age, postnatal age, postconceptional age, birth weight, and current body weight were correlated with pharmacokinetic parameters in neonates, especially preterm infants. Comorbidity characteristics affecting pharmacokinetics in critically ill neonates were perinatal asphyxia, hypoxic ischemic encephalopathy, patent ductus arteriosus (PDA), and renal dysfunction. Administration of indomethacin or ibuprofen in neonates with PDA was associated with the reduced clearance of renally excreted drugs such as vancomycin and amikacin. Therapeutic hypothermia and extracoporeal membrane oxygenation were influencing factors on pharmacokinetic parameters in critically ill neonates. Dosing adjustment and careful monitoring according to the factors affecting pharmacokinetic variability is required for safe and effective pharmacotherapy in neonatal intensive care unit.

• 생명과학회지
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• 제9권3호
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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.

• 약학회지
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• 제59권3호
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• pp.92-97
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• 2015

KIOM-MA128 is a novel Korean herbal medicine with anti-atopic, anti-inflammatory and anti-asthmatic effects. This article presents the first pharmacokinetic study on KIOM-MA128. The purpose of this study was to characterize a pharmacokinetic characteristic of matrine, a potential marker of KIOM-MA128, in rats using population pharmacokinetic model. 1, 2 and 8 g/kg of KIOM-MA128 were administered to rats orally and plasma concentrations of matrine was determined by HPLC-MS/MS. Non-compartmental analysis (NCA) was performed using Phoenix$^{(R)}$ and pharmacokinetic model was built using NONMEM$^{(R)}$. This model was validated with internal validation which is visual predictive check (VPC) and bootstrap. The NCA result of matrine showed that $C_{max}$ was 294.24, 552.22 and 868.65 ng/ml, $AUC_{inf}$ was 1273.05, 2724.76 and $9743.25ng{\cdot}hr/ml$ and $T_{max}$ was 1, 1.3 and 2.3 hr for the doses of 1, 2, and 8 g/kg, respectively. The rat plasma concentrations were described very well with one-compartment model. Pharmacokinetic model for matrine was successfully developed and evaluated. Finally, our model is helpful to understand pharmacokinetic characteristic of KIOM-MA128.

• 한국임상약학회지
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• 제26권2호
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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.

• Asian-Australasian Journal of Animal Sciences
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• 제33권4호
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• 약학회지
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• 제57권1호
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• pp.32-36
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• 2013

The purpose of this study was to determine the influence of assay error for improved pharmacokinetic modeling and simulation of vancomycin on the Bayesian and nonlinear least squares regression analysis in 24 Korean gastric cancer patients. Vancomycin 1.0 g was administered intravenously over 1 hr every 12 hr. Three specimens were collected at 72 hr after the first dose from all patients at the following times, at 0.5 hr before regularly scheduled infusion, at 0.5 hr and 2 hr after the end of 1 hr infusion. Serum vancomycin levels were analyzed by fluorescence polarization immunoassay technique with TDX-FLX. The standard deviation (SD) of the assay over its working range had been determined at the serum vancomycin concentrations of 0, 20, 40, 60, 80 and $120{\mu}g/ml$ in quadruplicate. The polynomial equation of vancomycin assay error was found to be SD $({\mu}g/ml)=0.0224+0.0540C+0.00173C^2$ ($R^2=0.935$). There were differences in the influence of weight with vancomycin assay error on pharmacokinetic parameters of vancomycin using the nonlinear least squares regression analysis but there were no differences on the Bayesian analysis. This polynomial equation can be used to improve the precision of fitting of pharmacokinetic models to optimize the process of model simulation both for population and for individualized pharmacokinetic models. The result suggests the improvement of dosage regimens for the better and safer care of patients receiving vancomycin.

• 한국의료질향상학회지
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• 제7권2호
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• pp.168-179
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• 2000

Background : Economic evaluation of clinical pharmacokinetic consultation services for theophylline, which is being widely used recently, is considered in patients for both proper care and cost efficiency. Mathods : This is a cost-benefit analysis of clinical pharmacokinetic consultation service for theophylline. Trial groups were chosen from 2 general hospitals which was performing clinical pharmacokinetic consultation- services in 1998. Control group was chosen from another one general hospital. The analysis includes 25 patients (sample patients) for trial group and 17 patients for control group. Results : On the basis of incremental analysis, it is estimated that the total (direct and indirect) annual costs of the clinical, pharmacokinetic services of theophylline for the patients in the trial group was about \65 million, whereas total annual benefits from those services was estimated to be about \551 million. The net benefits incurred to the sample patients, thus calculated, was about \485 million per year. In the analysis, we assumed that indirect benefits accruing to those services were non-existent. If that amount was included, the estimated net benefits would be much greater than the calculated one. Conclusion : We found that clinical pharmacokinetic consultation services for theophylline could produce more marginal benefits than marginal costs by those services from the social point of view. More controlled prospective trial in the future would be helpful for affirmation of the results of this study.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.389-394
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• 1998

Cyclosporine (CsA) is a major immunosuppressive drug used widely to prevent organ allograft rejection. fits potential organotoxicity by prolonged use is known to cause both direct tissue damage and indirect pharmacokinetic interactions with other drugs. This study was performed to determine the effect of nicardipine (NCP) on the pharmacokinetic parameters of CsA in Sprague-Dawley rats. Each rat was administered with CsA in saline-treated group or in NCP-treated group which was pretreated with NCP (5 mg/kg/12 hours, i.p.) for 6 days. The plasma CsA concentration were analyzed by reversed HPLC: UV system at 0.5, 1, 2, 4, 6, and 8 hours after bolus injection of CsA (10 mg/kg). Pharmacokinetic parameters (mean$\pm$ SD, n=7) such as initial plasma concentration (C(0)), mean residence time (MRT), steady-state volume of distribution (Vdss), terminal half-life (t$\frac{1}{2}$($\beta$)) and plasma clearance (CLp) of CsA in each groups (saline-group vs NCP-group) were determined as follows: C(0) (5.66$\pm$ 1.98 vs 17.98$\pm$2.36, p<0.01); Vdss (2.68$\pm$ 1.6 vs 0.94 $\pm$ 0.25, p<0.01); CLp (0.53 $\pm$0.18 vs 0.21 $\pm$0.06, p<0.01). Therefore, Our results indicate that nicardipine significantly affects the pharmacokinetic parameters of cyclosporme, especially C(0), Vdss, and CLp in NCP-treated group. We suggest that the significant pharmacokinetic interaction between cyclosporine and nicardipine should be considered and cyclosporine level should be closely monitored and dosage reduction made as necessary in clinical situation that was coadministered with CsA and NCP.

• 약학회지
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• 제43권2호
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• pp.160-168
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• 1999

The purpose of this study was to determine pharmacokinetic parameters of vancomycin using peak and trough plasma level (PTL) and Bayesian analysis in 20 Korean normal volunteers, 16 gastric cancer and 12 lymphoma patients and also using the compartment model dependent (nonlinear least squares regression: NLSR) and compartment model independent (Lagrange) analysis in 10 ovarian cancer patients. Nonparametric expected maximum (NPEM) algorithm for calculation of the population pharmacokinetic parameters was used, and these parameters were applied for clinical pharmacokinetic parameters by Bayesian analysis. Vancomycin was administered as dose of 1.0 g every 12 hrs for 3 days by IV infusion over 60 minutes in normal volunteers, gastric cancer and lymphoma patients. Population pharmacokinetic parameters, K and Vd in gastric cancer and lymphoma patients using NPEM algorithm were $0.158{\pm}0.014{\;}hr^{-1},{\;}0.630{\pm}0.043{\;}L/kg{\;}and{\;}0.131{\pm}0.0261{\;}hr^{-1},{\;}0.631{\pm}0.089{\;}L/kg$ respectively. The K and Vd in gastric cancer and lymphoma patients using Bayesian analysis were $0.151{\pm}0.027,{\;}0.126{\pm}0.056{\;}hr^{-1}{\;}and{\;}0.62{\pm}0.105,{\;}0.63{\pm}0.095{\;}L/kg$. The K and Vd in ovarian cancer patient using the NLSR and Lagrange analysis were $0.109{\pm}0.008,{\;}0.126{\pm}0.012{\;}hr^{-1}{\;}and{\;} 0.76{\pm}0.08,{\;}0.69{\pm}0.19{\;}L/kg$, respectively. It is necessary for effective dosage regimen of vancomycin in cancer patients to use these population parameters.