Synthesis and In-vitro Evaluation of N4-Amino Acid Derivatives of Cytarabine for Improving the Oral Delivery of Cytarabine

한효경,홍준희,ming-ji jin 한국약제학회 2008 Journal of Pharmaceutical Investigation Vol.38 No.4

The present study aimed to investigate the in-vitro characteristics of N4-amino acid derivatives of cytarabine for the oral delivery of cytarabine. After the synthesis of L-Ile-cytarabine, L-Leu-cytarabine and L-Arg-cytarabine, the gastrointestinal stability of each prodrug was examined using artificial gastric juice and intestinal fluids. The cellular uptake characteristics of prodrugs were also examined in Caco-2 cells. While L-Ile-cytarabine and L-Leu-cytarabine appeared to be stable in all the tested biological media during 4-hr incubation, L-Arg-cytarabine was rapidly disappeared within 5 min. Accordingly, the cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine was significantly higher than that of its parent drug, cytarabine in Caco-2 cells but the cellular uptake of L-Arg-cytarabine was similar to that from its parent drug. The cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine appeared to be saturable as drug concentration increased from 0.4 to 4 mM. Collectively, L-Ile-cytarabine and L-Leu-cytarabine could be promising candidates to improve the oral absorption of cytarabine via a saturable transport pathway.

Role of Transporters in Drug Interactions

한효경 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

Over the past few decades, a tremendous amount of work has been done on the molecular characterization of transport proteins in animals and humans, leading to a better understanding of the physiological roles of a number of transport proteins. Furthermore, there is increasing preclinical and clinical evidence to support the importance of transport proteins in the pharmacokinetics and toxicokinetics of a wide variety of structurally diverse drugs. As a consequence, the degree of expression and functionality of transport proteins may directly affect the therapeutic effectiveness, safety and target specificity of drugs. Recently, there has also been increased awareness about potential drug-drug, drug-herb and drug-food interactions involving transporters. Traditionally, a change in metabolic clearance of a drug, particularly via cytochrome P450-mediated metabolism, has been considered the cause of many clinically important drug interactions. However, increasing evidence suggests that some drug interactions result from changes in the activity and/or expression of drug transporters. Accordingly,assessment of the clinical relevance of transporter-mediated drug interactions has become a regulatory issue during the drug approval process and also the evaluation of drug interaction potential has become an integral part of risk assessment during drug development processes. Therefore, this review will highlight the role of some selected drug transporters in drug interactions,as well as their clinical implication.

니페디핀과 퀠세틴의 토끼에서의 약물동태학적 상호작용

한효경,이일권,최준식 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.4

The pharmacokinetics of nifedipine was studied after oral coadministration of nifedipine (5 ㎎/㎏) with quercetin (1.5, 7.5, 15 and 30 ㎎/㎏, respectively) and 0.5 h or 3days pretreatment with quercetin (1.5 and 7.5㎎/㎏) in rabbits. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the plasma concentration of nifedipine, but not significant in coadministraiton. The area under the plasma concentration-time curve (AUC) and the peak concentration (Cr.) of nifedipine pretreated with quercetin were increased significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) compared to the control. By coadministration of quercetin, only 7.5 ㎎/㎏ of quercetin increased plasma AUC and Cmax of nifedipine significantly (p<0.05) compared to the control. Plasma AUC of intravenous nifedipine (1 ㎎/㎏) is 4235 ± 1192 ng/ml · hr. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the absolute bioavailability (AB%) of nifedipine to 23.9 - 29.2% compared to the control (17.8%). Coadministration of quercetin showed no significant effect on the AB% of nifedipine except for 7.5 ㎎/㎏. It is suggested that quercetin alters disposition of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered chronically with quercetin in a clinical situation.

이성체/전구체 의약품의 안전성 및 유효성 평가 동향

한효경 한국에프디시규제과학회(구 한국에프디시법제학회) 2010 한국에프디시법제학회 학술대회 Vol.2010 No.1

분무열분해로 합성된 전이금속 기반의 저 루테늄 산성전해질용 수전해 촉매 개발

한효경,박세규 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0

기존의 PEMWE (Proton Exchange Membrane Water Electrolysis) 촉매에는 산성 전해질과 고전위 조건에서도 견딜 수 있도록 Ir과 같은 귀금속을 주로 사용하었다. 그러나 귀금속을 사용하기 때문에 가격이 비싸다는 문제가 있었다. 따라서 귀금속의 양을 줄이면서도 산성전해질에서 부식되지 않는 촉매의 개발이 중요하다. 본 연구에서는 PEMWE용 비 이리듐, 저 귀금속 촉매로써 RuCoOx/rGO 복합체를 초음파분무열분해(Ultrasonic Spray Pyrolysis)방법과 후 열처리를 통해 합성하였다. 합성한 복합체는 Ru과 Co의 결합을 강하게 하여 촉매를 안정하게 하기 위해 공기 분위기에서 열처리 해준다. 특성 분석과 전기화학적 평가는 XRD, XPS, TEM, LSV로 시행하였다. 분석 결과, 300 °C에서 열처리한 촉매가 가장 우수한 수전해 활성을 보였다. 개발한 촉매는 산성 전해질에서 305 mV (@10mA/cm2)의 과전압을 보였으며, Ir black의 과전압(309 mV (@10mA/cm2))과 비교할 만하다. 또한, 3000 cycle의 가속 내구성 테스트 후에 Ir black은 성능이 크게 떨어진 반면(초기 성능의 10% 이하), 개발 촉매는 초기 성능의 약 70% 를 유지하며 좋은 안정성을 보였다.

Acyclonucleoside류의 합성(5)

한효경,이미경,양재욱,천문우,정원근 서울대학교 1989 藥學論文集 Vol.14 No.1

청년과 노인 연령군에 따른 척주세움근에 대한 마이오톤의 측정자 간, 측정자 내 신뢰도

한효경 ( Hyo-gyeong Han ),최예주 ( Ye-ju Choe ),정성호 ( Seong-ho Jeong ),이나경 ( Na-kyung Lee ) 대한통합의학회 2021 대한통합의학회지 Vol.9 No.1

Purpose : The purpose of this study is to examine inter-and intra-rater reliabilities of myotonometric measurements of tone, elasticity and stiffness for the erector spinae muscles of the young and the elderly populations. Methods : A total of 102 (69 young adults from K university and 33 older adults from the D community center in Daejeon) were enrolled in this study. The two different raters measured each side of the erector spinae muscles at prone position. After each rater performed first measurement for a subject, 30 minutes of rest was given. The same rater then repeated the second myometric measurement on the subject. The collected data on the tone, elasticity, and stiffness of the erector spinae were analyzed using intraclass correlation coefficient (ICC) to determine inter- and intra- rater reliabilities. Results : The inter-and intra-rater reliabilities of the myotonometric measurement of the erector spinae for the total subjects were excellent (ICC > 0.9, p < 0.001). Within each of the elderly group and the young group, inter- and intra-rater reliabilities were also excellent (ICC > 0.8~0.9 / p < 0.001, ICC > 0.75~0.9 / p < 0.001, each). Conclusion : The measurement of muscle tone, elasticity, and stiffness for the erector spinae muscles using the myotonometer had excellent reliability. It was confirmed that a highly reliable myometric measurement on the erector spinae can be obtained regardless of whether it is from young or elderly people. This suggests that the myotonometer can be a useful tool to measure muscular properties of the erector spinae of the young and old as an evaluative instrument.

Role of Monocarboxylic Acid Transporters in the Intestinal Absorption of NSAIDs

한효경 ( Hyo Kyung Han ) 전남대학교 약품개발연구소 2005 약품개발연구지 Vol.14 No.-

Integrated Evaluation of Biopharmaceutical Properties and Its Impact on New Drug Discovery

한효경 ( Hyo Kyung Han ) 전남대학교 약품개발연구소 2004 약품개발연구지 Vol.13 No.-

Menadione serves as a substrate for P-glycoprotein: implication in chemosensitizing activity

오석정,한효경,강건욱,이영주,이무열 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.4

Based on its chemosensitizing effect, we questionedwhether menadione is an inhibitor or a substrate ofP-glycoprotein (P-gp). To test this hypothesis, we assessedthe effect of menadione on P-gp activity and examined theP-gp-dependency of cellular accumulation and cytotoxicityof menadione as well. Treatment with menadione resultedin the concentration-dependent increase of rhodamine 123(Rh123) accumulation in P-gp-overexpressing MDCKII/MDR1 and NCI/ADR-RES cells, suggesting that menadioneinhibits Rh123 extrusion by P-gp. Compared withMDCKII or MCF-7, intracellular distribution of [3H]-menadione was significantly lower in MDCKII/MDR1 orNCI/ADR-RES cells, which could be restored by the P-gpinhibitors, verapamil and quinidine. Consistent with theseresults, MDCKII/MDR1 or NCI/ADR-RES cells weremore resistant to the cytotoxicity of menadione thanMDCKII or MCF-7 cells, respectively. Such resistance wasabolished by the combined treatment of verapamil andquinidine in NCI/ADR-RES cells. Our study identifiedmenadione as a substrate of P-gp, which presumably, actsas the mechanism for the chemosensitizing effect. Menadionemay be a promising chemotherapeutic enhancer byits ability of circumventing drug resistance, in addition toits own anti-cancer activity.