• Biomolecules & Therapeutics
• /
• v.5 no.3
• /
• pp.284-291
• /
• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• Journal of Pharmaceutical Investigation
• /
• v.25 no.3
• /
• pp.249-264
• /
• 1995

Although liposome has many advantages as a pharmaceutical dosage form, its application in the industrial field has been limited because of some problems such as preparation method, reproducibility, scale-up, stability and sterilization etc. Liposomes prepared by microemulsification method had defined size, narrow size distribution, reproducibility and high entrapment efficiency. For enhancing the stability, the dry form of liposome was recommended. These types of liposome are proliposome and freeze-dried liposome. The liposome must have some properties for preparing of freeze-dried liposome; small size $(50{\sim}200\;nm)$, narrow size distribution and cryoprotectant. In this experiment, the liposomes containing 5-Fluorouracil(5-FU) and its prodrug(pentyl-5-FU-1-acetate; PFA, hexyl-5-FU-1-acetate; HFA) were made with soybean phosphatidylcholine, cholesterol, stearylamine(SA) and dicetyl phosphate(DCP) employing hydration method or microemulsification method using $Microfluidizer^{TM}$. Both or liposome types were MLV and MEL. After preparation, freeze drying and rehydration were performed. In the process of freezing, trehalose(Tr) was added as a cryoprotectant. Their evaluation methods were as follows; entrapment efficiency, mean particle size and size distribution, dissolution test, retain of entrapment efficiency and turbidity after freeze-drying. The results are summarized as belows. The entrapment efficiency of 5-FU was dependent on total lipid concentration and cholesterol content but that of PFA and HFA was decreased when cholesterol was added. When DCP and SA were added, entrapment efficiency was decreased. As the partition coefficient of drug was increased, entrapment efficiency was increased. Under the same condition, entrapment efficiency of MEL is similar to that of MLV. The mean particle size and size distribution of MEL were smaller than those of MLV. Dissolution rates of drug from both liposome types were comparatively similar. Dissolution rates of drugs with serum and liver homogenate were faster than without these material. After preparation of liposome, free drug was removed efficiency by Dowex 50W-X4. When liposome was freeze-dried and then rehydrated in the presence of Tr, characteristics of liposome were maintained well in MEL than MLV. Tr Was used successfully as a cryoprotectant in the process of freeze drying and the optimal ratio of Tr:Lipid was 4:1(g/g).

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1996.04a
• /
• pp.287-287
• /
• 1996

Long-circulating liposomes have prompted interests in using them as a drug delivery system. This improvements in delivery has been thought to be the results from sustained action of liposomes in plasma without RES uptake. Although methotrexate(MTX) has been one of the most widely used antineoplastc drug, its use was limited by prompt RES uptake. The purpose of this study was to prepare long-circulating liposomes for MTX using highly water-soluble polymer (PEG-PE). In vitro, release of MTX from liposomes in phosphate buffer (pH 7.4), rat liver homogenate, and rat plasma was investigated. The pharmacokinetics and organ distribution of fee drug, conventional and long-circulating liposomes were also compared with one another after intravenous administration to rats.

• Pediatric Infection and Vaccine
• /
• v.3 no.1
• /
• pp.66-74
• /
• 1996

There continues to be increasing the number of patients being treated for renal failure day by day due to lot of causes. It is prerequsite for the physician to have a proper understanding of drug use in patients with renal failure since kidney is the major route of elimination for many kinds of drugs and their metabolites. In order to provide practical guidelines for prescribing antibiotics, the literature has been reviewed, and summarized. The tables presented here are made by Dr. William M Bennett et al. and listed the specific pharmacokinetic information such as drug half life, serum levels, and drug removal during dialysis, plasma protein binding, volume of distribution.

• Journal of Preventive Medicine and Public Health
• /
• v.10 no.1
• /
• pp.25-33
• /
• 1977

The epidemiological informations on 1,828 cases of acute drug intoxication admmitted to the emergency rooms of 5 general hospitals, 4 in Seoul City and 1 in Incheon City from Jan. 1974 to Dec. 1974, were reviewed for statistical analysis. More detailed information on 796 cases from 3 hospitals were available in terms of the causative agent. The general findings obtained are as follows; 1. The sex ratio of the patient is 1.26 females to 1 male and this figure is almost consistent with the reports of previous authors. 49.7% of total cases were found in the age group of 20-29, which indicate the highest in percent distribution of age. 2. The incidence of acute drug intoxication was different by the season as the highest in summer and the lowest in winter. 3. As the cause of the intoxication, the attempted suicide occupied the single highest one with 91.7%. 4. The kind of causative agents varies with seasons as more economic poisons in the summer time and more drugs in the winter time.

• Proceedings of the Korean Society of Computer Information Conference
• /
• 2014.01a
• /
• pp.185-188
• /
• 2014

본 연구는 자재업체부터 마약류 생산 제약사 도매업체(물류) 대형병원까지의 전체 프로세스에 RFID 시스템을 구축하여 마약류의 도난 및 오남용을 방지하여 국민의 보건안전 및 의약품 관리강화를 도모하는 것으로 현재까지 기 구축된 제약사들의 RFID 시스템에서 기술적으로 고도화시킬 수 있는 방안을 도출하여 최적화된 현장적응형 RFID 서비스를 제공하고자 하는데 그 목적이 있다. 본 연구를 통하여 제약산업 내 제약사 도매업체 대형종합병원 의원에 대한 RFID 도입표준모델을 제시하고 Supply Chain의 유통 투명화를 위한 정보시스템 도입의 기반을 마련함으로써 제약산업 내 참여주체들간의 정보 신뢰성 제고는 물론 철저한 의약품 유통관리로 인한 건전한 의약품 소비문화를 정착시킬 수 있다.

• Archives of Pharmacal Research
• /
• v.26 no.7
• /
• pp.526-531
• /
• 2003

KR-31378 is a new drug candidate intended for the use in the prevention of ischemia-reperfusion damage. The objective of this preformulation study was to determine the physicochemical properties of KR-31378. The n-octanol to water partition coefficients of KR-31378 were 0.0504 at pH 3 and 0.8874 at pH 10. Accelerated stability of KR-31378 in solution and solid state was studied at 5, 40, $60^{\circ}C$. The stability testing indicated that the t90 for the drug in solid was estimated to be 2 years and 128.6 days at $25^{\circ}C$, while the that in aquesou solution was 68.6 days at $25^{\circ}C$. The KR-31378 was also found to be unstable under the relative humidity of 76%, probably because of the hygroscopic nature of the drug. In order to study compatibility of KR-31378 with typical excipients, potential change in differential scanning calorimetry spectrum was studied in 1:1 binary mixtures of KR-31378 and Aerosil, Avicel, Eudragit, lactose, PEG, talc, CMC, PVP, starch. As a result, CMC, PVP, and starch were found to be incompatible with KR-31378, indicating the addition of these excipients may complicate the manufacturing of the formulation for the drug. Particle size distribution of KR-31378 powder was in the size range of 9-93 $\mu$ m with the mean particle size of 37.9 $\mu$ m. The flowability of KR-31378 was apparently inadequate, indicating the granulation may be necessary for the processing of the drug to solid dosage forms. Crystallization of the drug with a number of organic solvents did not lead a crystalline polymorphism. In addition, dissolution of the drug from the powder was adequately rapid at $37^{\circ}C$ in water.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.1
• /
• pp.107-115
• /
• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.3835-3838
• /
• 2016

Background: Breast cancer is one of the most frequent cancer types within female populations. Silibinin is a chemotherapeutic agent ative against cancer. Niosomes are biodegradable, biocompatible, safe and effective carriers for drug delivery. Objective:To prepare nanoniosomal silibinin and evaluate its cytotoxicity inthe T-47D breast cancer cell line. Materials and Methods: Niosomes were prepared by reverse phase evaporation of a mixture of span 20, silibinin, PEG-2000 and cholesterol in chloroform and methanol solvent (1:2 v/v). The solvent phase was evaporated using a rotary evaporator and the remaining gel phase was hydrated in phosphate buffer saline. Mean size, size distribution and zeta potential of niosomes were measured with a Zetasizer instrument and then nanoparticles underwent scanning electron microscopy. The drug releasing pattern was evaluated by dialysis and the cytotoxicity of nanoniosomes in T-47D cells was assessed by MTT assay. Results: Particle size, size variation and zeta potential of the niosomal nanoparticles were measured as $178.4{\pm}5.4nm$, $0.38{\pm}0.09$ and $-15.3{\pm}1.3mV$, respectively. The amount of encapsulated drug and the level of drug loading were determined $98.6{\pm}2.7%$ and $22.3{\pm}1.8%$, respectively; released drug was estimated about $18.6{\pm}2.5%$ after 37 hours. The cytotoxic effects of nanoniosome were significantly increased when compared with the free drug. Conclusions: This study finding suggests that silibinin nanoniosomes could serve as a new drug formulation for breast cancer therapy.

• Journal of Biomedical Engineering Research
• /
• v.40 no.1
• /
• pp.7-14
• /
• 2019

The microencapsulation of nifedipine (NF) with 4 wt% of poly(${\varepsilon}-caprolactone$) (PCL)/polyvinylpyrollidone (PVP) or PCL/polyethylene glycol (PEG) was carried out by solvent evaporation method in oil in water emulsion system to investigate the effect of PVP and PEG addition on drug release behavior of the microcapsules. The PVA (emulsifier) concentration of 1.0 wt% was chosen for the formation of PCL capsule having an average size of $154{\pm}25{\mu}m$ due to nearly spherical shape with a narrow size distribution. As PCL/PVP and PCL/PEG ratios were raised from 10/0 to 6/4, the capsule size increased gradually from $154{\pm}25{\mu}m$ to $236{\pm}32{\mu}m$ and $248{\pm}56{\mu}m$, respectively. The drug release rate of PCL/PVP and PCL/PEG capsules increased dramatically from 0 to 4 h at the beginning and then reached the plateau region from 20 h. As the concentration of PVP or PEG increased, the amount of drug release increased, suggesting that the larger capsule size was attributed to the higher drug content. However, the drug release behavior remained almost constant. The PCL capsules exhibited no evidence of causing cell lysis or toxicity regardless of NF loading, implying that the microcapsules are clinically suitable for use as drug delivery systems.