Evaluation of Metabolism-Mediated Herb-Drug Interactions

나동희,Hye Young Ji,박은지,Myung Sun Kim,Kwang-Hyeon Liu,이혜숙 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

As the use of herbal medicines increases, the public health consequences of drug-herb interactions are becoming more significant. Herbal medicines share the same drug metabolizing enzymes and drug transporters, including cytochrome P450 enzymes (CYPs), glucuronosyltransferases (UGTs), and P-glycoprotein, with several clinically important drugs. Interactions of several commonly used herbal medicines, such as Ginko biloba, milk thistle, and St. John’s wort, with therapeutic drugs including warfarin, midazolam, alprazolam, indinavir, saquinavir, digoxin, nifedipine, cyclosporine, tacrolimus, irinotecan, and imatinib in humans have been reported. Many of these drugs have very narrow therapeutic indices. As the herb-drug interactions can significantly alter pharmacokinetic and pharmacodynamic properties of administered drugs, the drugs interacting with herbal medicines should be identified by appropriate in vitro and in vivo methods. A good understanding of the mechanisms of herb-drug interactions is also essential for assessing and minimizing clinical risks. In vitro methods are useful for providing mechanistic information and evaluating multiple components in herbal medicines. This review describes major factors affecting the metabolism of herbal medicines, mechanisms of herb-drug interactions mediated by CYPs and UGTs, and several in vitro methods to assess the herb-drug interactions. Finally, drug interactions of Ginkgo biloba and St. John’s wort, as representative herbal medicines, are described.

Effect of pH on the Formation of Acylated Octreotides by Poly(lactide-co-glycolide)

나동희 한국약제학회 2010 Journal of Pharmaceutical Investigation Vol.40 No.4

The formation of acylated peptide impurities in poly(lactide-co-glycolide) (PLGA) formulations is one of the major challenges to the development of successful sustained-release product. Octreotide, synthetic analogue of somatostatin, has been identified to be acylated in PLGA microsphere formulations. The purpose of this study was to investigate the pH effect on the formation of acylated octreotides by PLGA. In the incubation with PLGA in 0.1 M phosphate buffer at pH 7.4, approximately 98% of octreotide adsorbed to PLGA through 14 days and 66.3% of acylated octreotides were produced after 42 days, whereas the interaction of octreotide with PLGA was significantly inhibited in the incubation at pH 4, in which the acylated octreotides were observed to be 9.2% after 42 days. In the interaction study at pH 4.1-7.4, the production of acylated octreotides was demonstrated to be dependent on environmental pH. Below pH 5.0, the acylation of octreotide was significantly inhibited. This study indicates that the pH is the major factor for the formation of acylated octreotide in PLGA formulations.

Analytical Methods for the Quality Control of Biopharmaceuticals

나동희 한국분석과학회 2018 학술대회논문집 Vol.2018 No.11

Treatment Outcomes and Risk Factors for In-Hospital Mortality in Patients with Acute Aortic Occlusion

나동희,황덕비,박수진,김형기,허승 대한혈관외과학회 2018 Vascular Specialist International Vol.34 No.2

Purpose: The aims of the present study are to determine the outcomes after acute aortic occlusion (AAO) and analyze the risk factors for in-hospital mortality. Materials and Methods: We retrospectively analyzed 24 patients who were diagnosed with AAO from 2002 to 2017 in our registered data. Demographic and radiologic characteristics of AAOs were retrospectively collected. Perioperative treatment outcomes including in-hospital mortality were also assessed and the risk factors of in-hospital mortality were analyzed. Results: The median symptom duration was 21 hours. Five patients had complete paraplegia and 10 patients (41.7%) were initially evaluated for central nervous system disorders instead of acute arterial occlusion. The etiology was determined to be aortoiliac thrombosis in 17 patients (70.8%) and embolic occlusion in 7. Surgical revascularization was performed in 23 patients, and one patient did not receive any treatment. The overall in-hospital mortality was 34.8% (8/23) and 30- day mortality was 26.1%. In the univariate analysis, age (P=0.040), preoperative renal insufficiency (serum creatinine over 1.5 mg/dL at the time of presentation) (P=0.008), postoperative acute kidney injury (need for dialysis or an increase in serum creatinine of >50.0% within 48 hours) (P=0.006), combined external iliac artery occlusion (P=0.019) and combined bilateral internal iliac artery occlusion (P=0.039) were associated with in-hospital mortality. Conclusion: A substantial number of AAO patients were initially evaluated for a central nervous system lesion, which led to a delay in diagnosis. Thus, vascular examinations should always be performed in every patient presenting with lower limb neurologic deficits. Age, perioperative renal function, and combined iliac artery occlusion were associated with the prognosis of AAOs.

Capillary Electrophoresis 와 MALDI - TOF 질량분석기를 이용한 면역독소의 분석 연구

나동희(Dong Hee Na),조정관(Cheong Kwan Cho),김용석(Yong Suk Kim),이강춘(Kang Choon Lee) 한국약제학회 1998 한국약제학회 총회 및 학술대회 요지집 Vol.- No.28

N/A N/A

PEGylation 기술을 이용한 단백질 의약품 개발

나동희(Dong Hee Na) 한국생물공학회 2011 KSBB Journal Vol.26 No.4

PEGylation, the attachment of polyethylene glycol (PEG) to proteins, is currently main technology for improving efficacy of protein drugs. This technology can prolong the plasma half-life, augment the in vivo stability, and diminish the immunogenicity of therapeutic proteins. Therefore, PEGylated proteins have the enhanced therapeutic efficacy and the reduced undesirable effects versus their native therapeutics. Since the first PEGylated protein product appeared on the market in the early 1990s, currently ten PEGylated protein products have been launched. These marketed drug products have proved the applicability and safety of the PEGylation technology. This review presents overview of PEGylation technology and addresses characteristics of PEGylation methods applied for the development of several protein drugs.

Simultaneous Determination of Cysteamine and Cystamine in Cosmetics by Ion-Pairing Reversed-Phase High-Performance Liquid Chromatography

김예진,나동희 한국독성학회 2019 Toxicological Research Vol.35 No.2

Cysteamine has been used in cosmetics as an antioxidant, a hair straightening agent, and a hair waving agent. However, recent studies indicate that cysteamine can act as an allergen to hairdressers. The objective of this study was to develop and validate a simple and effective reversed-phase high-performance liquid chromatography (RPHPLC) method for the measurement of cysteamine and its dimer, cystamine. Sodium 1-heptanesulfonate (NaHpSO) was used as an ion-pairing agent to improve chromatographic performance. Separation was performed on a Gemini C18 column (250 mm × 4.6 mm, 5 μm particle size) using a mobile phase composed of 85:15 (v/v) 4 mM NaHpSO in 0.1% phosphoric acid:acetonitrile. UV absorbance was monitored at 215 nm. The RP-HPLC method developed in this study was validated for specificity, linearity, limit of detection, limit of quantitation, precision, accuracy, and recovery. Cysteamine and cystamine were chromatographically resolved from other reducing agents such as thioglycolic acid and cysteine. Extraction using water and chloroform resulted in the recovery for cysteamine and cystamine ranging from 100.2-102.7% and 90.6-98.7%, respectively. This validated RP-HPLC method would be useful for quality control and monitoring of cysteamine and cystamine in cosmetics.

Palmitoylation of octreotide for incorporation into poly(amidoamine) dendrimers

박은지,나동희 한국약제학회 2014 Journal of Pharmaceutical Investigation Vol.44 No.2

Poly(amidoamine) (PAMAM) dendrimers arenano-sized carrier molecules with tremendous promise inpolymeric drug delivery systems. The purpose of this studywas to prepare and characterize palmitoyl-octreotideincorporatedPAMAM dendrimers. As octreotide is hydrophilic,it was difficult to be incorporated into PAMAMdendrimers. This study demonstrated that the conjugation ofpalmitic acid (palmitoylation) was effective for the incorporationof octreotide into PAMAM dendrimers. The sitespecificpalmitoylation at the N-terminal amine of octreotidewas successfully performed by a reversible protectionapproach using maleic anhydride, and the conditions for theproduction of the final product were optimized. The incorporationyield of palmitoyl-octreotide into PAMAM dendrimerswas significantly higher than that of octreotide. Thepalmitoyl-octreotide-incorporated PAMAM dendrimer hasa potential as a new drug delivery system for somatostatintherapeutics.

Simultaneous Determination of Quercetin and its Glycosides from the Leaves of Nelumbo nucifera by Reversed-Phase High-Performance Liquid Chromatography

구현률,최재수,나동희 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.2

The purpose of this study was to develop reversed-phase HPLC method for the simultaneous determination of the flavonoids from the leaves of Nelumbo nucifera, which have been known to exhibit antioxidant, anti-HIV, antihyperlipidemic and antiobesity effects. HPLC separation was achieved on C18 column using gradient elution with mobile phase consisting of acetonitrile-water containing 0.1% formicacid. The separated peaks were identified by electrospray ionization mass spectrometry. The HPLC method was validated and applied for the simultaneous determination of the bioactive flavonoids from the leaves of Nelumbo nucifera. In the methanol extract, six flavonoids, quercetin, rutin, quercetin 3-O-β-D-galactopyranoside (Qc-3-Gal), quercetin 3-O-β-D-glucopyranoside (Qc-3-Glc), quercetin 3-O-β-Dglucuronide (Qc-3-Gln) and quercetin 3-O-α-arabinopyranosyl-(1→2)-β alactopyranoside (Qc-3-AraGal), were identified. Among them, Qc-3-Glc and Qc-3-Gln were found to be major component in the methanol extract of Nelumbo nucifera leaves.

Recent progress in dendrimer-based nanomedicine development

김예진,박은지,나동희 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.6

Dendrimers offer well-defined nanoarchitectureswith spherical shape, high degree of molecular uniformity,and multiple surface functionalities. Such unique structuralproperties of dendrimers have created many applicationsfor drug and gene delivery, nanomedicine, diagnostics, andbiomedical engineering. Dendrimers are not only capableof delivering drugs or diagnostic agents to desired sites byencapsulating or conjugating them to the periphery, butalso have therapeutic efficacy in their own. When comparedto traditional polymers for drug delivery, dendrimershave distinct advantages, such as high drug-loadingcapacity at the surface terminal for conjugation or interiorspace for encapsulation, size control with well-definednumbers of peripheries, and multivalency for conjugationto drugs, targeting moieties, molecular sensors, andbiopolymers. This review focuses on recent applications ofdendrimers for the development of dendrimer-basednanomedicines for cancer, inflammation, and viral infection. Although dendrimer-based nanomedicines still facesome challenges including scale-up production and wellcharacterization,several dendrimer-based drug candidatesare expected to enter clinical development phase in thenear future.