진네트정(세푸록심 250 mg)에 대한 베아세프정의 생물학적 동등성

이윤석,강찬순,박은석,지상철 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

ABSTRACT-The bioequivalence of “Bearcef tablet”(Daewoong Pharmaceutical Co.), containing 250 mg cefuroxime (as cefuroxime axetil), in reference to“Zinnat tablet”(Glaxo Wellcome Korea Co.) was evaluated in 16 normal volunteers (age 21∼29 yrs) following the oral administration. After one tablet was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was quantitated with an HPLC method. AUC, C_max and T_max were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, C_max and T_max between two products were 6.92%, 3.49% and 5.26%, respectively. The powers for AUC, C_max and T_max were >90%, >90% and 89.0%, respectively. Confidence intervals for these parameters were all within ±20%. Judging based on the above results, “Bearcef tablet”is regarded to be bioequivalent to “Zinnat tablet”.

SMEDDS를 이용한 난용성 약물의 용출율 향상

김계현,이윤석,배준호,지상철,박은석 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

ABSTRACT-A self-microemulsifying drug delivery system (SMEDDS) was developed to enhance the solubility and dissolution rate of poorly water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The system was optimized by evaluating the solubility of DDB and the microemulsion existence range after the preparation of microemulsions with varying compositions of triacetin and surfactant-cosurfactant mixtures (Labrasol as surfactant (S) and the combination of Transcutol, Cremophor RH 40 and Plurol oleique as cosurfactant (CoS)). SMEDDS in this study markedly improved the solubility of DDB in water up to 10 mg/ml and the size of the o/w microemulsion droplets measured by dynamic light scattering showed a narrow monodisperse size distribution with an average diameter less than 50nm. The microemulsion existing range is increased proportional to the ration of S/CoS, however, it decreased remarkably as the oil content was more than 20%. In vitro dissolution study of SMEDDS showed a significantly increased dissolution rate of DDB in water (>12 fold over DDB powder), and SMEDDS also had significantly greater permeability of DDB in Caco-2 cell compared to powders.

석청(Mad-honey) 복용 후 유발된 부정맥 1예

김용철,김남호,김승환,최준호,박은미,이상재,이은미,유남진,윤경호,오석규,정진원 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

석청에 포함된 grayanotoxin에 의해 독성 작용이 나올 수 있으며, 이러한 독성 작용은 일반적으로 24시간 이내 저절로 회복된다. 최근에 본 저자들은 석청 복용 후 발생한 심실빈맥을 경험하였기에 보고하는 바이다. 49세 남자가 호흡곤란으로 내원하였으며, 내원당시 분당 40회 정도의 동성 서맥이 관찰되었고, 수액을 투여하던 중 심실 빈맥이 발생하였다. 항부정맥제를 투여 후 정상 동율동으로 전환되었으며, 특별한 이상 없이 4일 후 퇴원하였다. Mad-honey intoxication caused by the consumption of honey producted from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The toxic effects of mad-honey poisoning are rarely fatal and generally last for no more than 24 hours. We experienced one case, a 49 years-old man who presented with dyspnea after ingestion of mad-honey. He showed marked sinus bradycardia with < 40 beats per minute on admission. The cardiac rhythm was changed to ventricular tachycardia immediately. These features resolved completely in 24 hours with continuous infusion of amiodarone(600 mg per day) and fluids. We report the case of intoxication of mad-honey as a presentation of fatal cardiac arrhythmia.

Analysis of Acamprosate in Beagle Dog Plasma by LC-MS-MS

Rhee, Yun-Seok,Park, Jeong-Hwa,Park, Seok,Park, Chun-Woong,Ha, Jeong-Myung,Jeong, Ki-Woo,Lee, Dong-Soo,Park, Eun-Seok 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.8

A rapid, sensitive, and specific analytical method was developed and validated to quantify acamprosate calcium in beagle dog plasma. The method employs a single plasma protein precipitation, and the analytes are separated by chromatography on an Acquity UPLC HSS T3 column and analyzed by mass spectrometry in the multiple reaction monitoring (MRM) mode. The method has a chromatographic run time of 1.25 min and a linear calibration curve over the range 200-10000 ng/mL ($r^2$ > 0.9994). The intra-day and inter-day accuracy and precision were within 10.0% for the analyte. Acamprosate was stable during all sample storage, preparation, and analytical periods. This method was employed in a pharmacokinetic study of an acamprosate 333 mg enteric-coated tablet in 8 male beagle dogs that received single 666 mg doses (333 mg $\times$ 2 tablets). The proposed method enables identification and quantification in pharmacokinetic studies of acamprosate in beagle dog plasma.

Characterization of Monolithic Matrix Patch System Containing Tulobuterol

Rhee, Yun-Seok,Kwon, Seok-Young,Park, Chun-Woong,Choi, Na-Young,Byun, Woo-Jin,Chi, Sang-Cheol,Park, Eun-Seok 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.8

The aim of this study was to investigate the effect of the functional groups in acrylic adhesive on tulobuterol uptake, release rate and permeation rate across rat dorsal skin. In addition, the relationship between these parameters was identified in order to formulate the monolithic matrix patch system. Seven acrylate pressure sensitive adhesives were used in this study with three different functional groups as follows: (1) no functionality (DT-4098), (2) hydroxyl group (DT-2287, DT-2510, DT-2525, DT-2516), and (3) carboxyl group (DT-2353, DT-2852). Tulobuterol-uptake in PSA was determined by the drug-uptake method. The amount of tulobuterol-uptake in acrylic polymers with a carboxyl group was higher than those in acrylate pressure sensitive adhesives with either a hydroxyl group or a nonfunctional group. The release rate of tulobuterol from the monolithic patches was evaluated and DT-2353 and DT-2852, which contained a carboxyl group, showed lower release rates of tulobuterol than the other acrylate pressuresensitive adhesives. The skin permeation of tulobuterol was investigated using excised rat dorsal skin and the permeation rate of tulobuterol from DT-2353 and DT-2852 was also lower than the other acrylate pressure sensitive adhesives. Taking into consideration the relationship between all the parameters, pressure sensitive adhesives can be categorized into two groups: those containing a carboxylic acid functional group and those containing a non-carboxylic group. These results indicate that there was an interaction between the secondary amino group of tulobuterol and the carboxyl group of the acrylate polymer. Therefore, we suggest that a drug's chemical structure and functional groups in pressure sensitive adhesives must be considered in order to formulate a transdermal patch system.

Investigation of the Relationship Between In Vitro and In Vivo Release Behaviors of Acamprosate from Enteric-Coated Tablets

Yun-Seok Rhee,Seok Park,Tae-Won Lee,Chun-Woong Park,Tae-Young Nam,Tack-Oon Oh,Ji-Woong Jeon,Dong-Soo Lee,Eun-Seok Park 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6

Acamprosate calcium is a highly soluble drug with low permeability that is used to maintain abstinence in alcohol-dependent patients. The aim of this study was to investigate the relationship between in vitro and in vivo behaviors of acamprosate from enteric-coated tablets. The in vitro release behavior of acamprosate tablets in pH 6.8 buffer solution was determined in three dissolution conditions, 50 and 150 rpm (paddle method) and 180 rpm (basket method). The results of this in vitro experiment indicated that acamprosate tablets hardly disintegrated, and drug dissolution was retarded despite the extremely hydrophilic nature of the drug. A single dose (333 mg×2 tablets) of each formulation was orally administered to four beagle dogs under fasting conditions, and the pharmacokinetic parameters were calculated. The mean AUC0-48, Cmax, Tlag and Tmax for the two types of tablets ranged from 41.5-53.6 μg·h/mL, 4.3-4.5 μg/mL, 2.0-2.5 h and 3.8-4.0 h, respectively. In conclusion, it is suggested that retarded drug release from the tablets and the low drug permeability may result in poor absorption and erratic bioavailability of this drug in humans.

In Vitro/in Vivo Relationship of Gabapentin from a Sustained-Release Tablet Formulation: A Pharmacokinetic Study in The Beagle Dog

Rhee, Yun-Seok,Park, Seok,Lee, Tae-Won,Park, Chun-Woong,Nam, Tae-Young,Oh, Tack-Oon,Jeon, Ji-Woong,Han, Sang-Beom,Lee, Dong-Soo,Park, Eun-Seok 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

The aim of this study was to examine the in vitro/in vivo relationship of the drug release behavior of a sustained-release formulation of gabapentin. The immediate-release formulation was used as the reference formulation. The dissolution test was employed using pH 1.2, 4.0, or 6.8 buffer solution, or water, to determine the in vitro release behaviors of gabapentin tablets. Gabapentin was released completely within 1 h from the immediate-release tablet and released for 12 h from the sustained-release tablet. A single dose (600 mg) of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. Although the sustained-release tablet did not disintegrate and had slow drug release characteristics, it showed similar pharmacokinetic parameters to the immediate-release tablet, which rapidly disintegrated and showed fast drug release. Thus, the in vivo release of gabapentin did not correlate with in vitro release of drug.

Investigation of the Relationship Between In Vitro and In Vivo Release Behaviors of Acamprosate from Enteric-Coated Tablets

Rhee, Yun-Seok,Park, Seok,Lee, Tae-Won,Park, Chun-Woong,Nam, Tae-Young,Oh, Tack-Oon,Jeon, Ji-Woong,Lee, Dong-Soo,Park, Eun-Seok 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6

Acamprosate calcium is a highly soluble drug with low permeability that is used to maintain abstinence in alcohol-dependent patients. The aim of this study was to investigate the relationship between in vitro and in vivo behaviors of acamprosate from enteric-coated tablets. The in vitro release behavior of acamprosate tablets in pH 6.8 buffer solution was determined in three dissolution conditions, 50 and 150 rpm (paddle method) and 180 rpm (basket method). The results of this in vitro experiment indicated that acamprosate tablets hardly disintegrated, and drug dissolution was retarded despite the extremely hydrophilic nature of the drug. A single dose ($333\;mg{\times}2$ tablets) of each formulation was orally administered to four beagle dogs under fasting conditions, and the pharmacokinetic parameters were calculated. The mean $AUC_{0-48}$, $C_{max}$, $T_{lag}$ and $T_{max}$ for the two types of tablets ranged from $41.5-53.6\;{\mu}g{\cdot}h/mL$, $4.3-4.5\;{\mu}g/mL$, 2.0-2.5 h and 3.8-4.0 h, respectively. In conclusion, it is suggested that retarded drug release from the tablets and the low drug permeability may result in poor absorption and erratic bioavailability of this drug in humans.

Effects of Vehicles and Enhancers on Transdermal Delivery of Clebopride

Rhee, Yun-Seok,Huh, Jai-Yong,Park, Chun-Woong,Nam, Tae-Young,Yoon, Koog-Ryul,Chi, Sang-Cheol,Park, Eun-Seok 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.9

The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 ${\mu}g/cm^2/h$. Overall, these results highlight the potential of clebopride formulation for the transdermal route.

Effect of Flavors on the Viscosity and Gelling Point of Aqueous Poloxamer Solution

Rhee, Yun-Seok,Shin, Young-Hee,Park, Chun-Woong,Chi, Sang-Cheol,Park, Eun-Seok The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.12

This study examined the effects of flavors, which are usually added to improve the appeal of pharmaceutical agents, on the viscosity and gelling point of 18% (w/w) aqueous poloxamer 407 solutions. Monoterpenes, esters, alcohols, aldehyde ketones and lactone type flavors were examined. The concentrations of flavor ranged from 0.1 to 1.0%(w/w). After adding a flavor to the aqueous poloxamer 407 solution, the viscosity of the solution was measured using a Brookfield viscometer, and the gelling point was determined from the viscosity vs. temperature plot. The gelling point of the aqueous poloxamer 407 solution decreased with increasing concentration of flavors except for coumarin, vanillin and ethylvanillin. Thermal analysis with DSC showed an interaction between the flavors and poloxamer 407. These results suggest that the flavors bind to the hydrophilic end chains of poloxamer 407, which increases the viscosity, causing gelation at lower temperatures.