• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.89-95
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• 2006

A selective and sensitive reversed-phase HPLC method for the determination of pentoxifylline in human serum was developed, validated, and applied to the pharmacokinetic study of pentoxifylline. Pentoxifylline and internal standard, chloramphenicol, were extracted from the serum by liquid-liquid extraction with dichloromethane and analyzed on a Luna CI8(2) column with the mobile phase of acetonitrile-0.034 M phosphoric acid (25:75, v/v, adjusted to pH 4.0 with 10 M NaOH). Detection wavelength of 273 nm and flow rate of 0.8 mL/min were used. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of the serum was 10 ng/mL, which was sensitive enough for pharmacokinetic studies of pentoxifylline. The overall accuracy of the quality control samples ranged from 89.3 to 92.7% for pentoxifylline with overall precision (% C.V.) being 4.1-9.2%. The relative mean recovery of pentoxifylline for human serum was 105.8%. Stability (stock solution, short and long-term) studies showed that pentoxifylline was not stable during storage. But three freeze-thaw cycles and extracted serum samples were stable. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of pentoxifylline in human serum samples for the pharmacokinetic studies of orally administered $Trental^{\circledR}$ tablet (400 mg pentoxifylline), demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제37권4호
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• pp.223-227
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• 2007

A rapid, simple and sensitive LC/MS/MS method for the determination of lercanidipine in human serum was validated and applied to the pharmacokinetic study of lercanidipine. Lercanidipine and internal standard, amlodipine, were extracted from human serum by liquid-liquid extraction with hexan-isoamyl alcohol (100: 1, v/v) and analyzed on a $Symmetry^{(R)}$ MS $C_{18}$ column with the mobile phase of acetonitrile-0.2% aqueous formic acid (70: 30, v/v). Using MS/MS with multiple reaction monitoring (MRM) mode, lercanidipine and amlodipine were detected without severe interferences from human serum matrix. Lercanidipine produced a protonated precursor ion ($[M+H]^+$) at m/z 612.3 and a corresponding product ion at m/z 280.0. Internal standard produced a protonated precursor ion ($[M+H]^+$]) at m/z 409.0 and a corresponding product ion at m/z 238.0. The ruggedness of this method was investigated using quality control (QC) samples. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient greater than 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the developed method ranged from 85.51 to 112.2% for lercanidipine with overall precision (% C.V.) being 3.56-13.1%. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of lercanidipine in human serum samples for the pharmacokinetic studies, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.401-409
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• 2009

Ketrorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug (NSAID) is required repeated administration due to its short blood half-life. To avoid dose-dependent side effects of KT, sustained-release pellets containing KT were prepared by coating with Eudragit$^{(R)}$ RS 100 and Eudragit$^{(R)}$ NE 30D. The in vitro and in vivo drug release behavior of KT from Eudragit$^{(R)}$ RS 100 and NE 30D coated pellet (SR-A), Eudragit$^{(R)}$ RS 100 coated pellet (SR-B) and conventional commercial immediate-release tablet (IR) was investigated. KT from SR-A and SR-B was slowly released over several hours, whereas IR showed rapid initial release in vitro. The pharmacokinetic study in vivo was performed by oral administration in beagle dogs. 5 mg IR was administered 3 times at intervals 5 hr. Five milligrams of IR was administered 3 times at intervals of 5 hr and 15 mg of SR-A and SR-B did once. After administering IR, KT concentration in blood showed high peak- trough fluctuation and stomach ulcer were discovered. On the other hand, SR-A and SR-B sustainedly released KT and reduced the occurrence of stomach ulcer. There sustained-release pellets will be effective system to minimize dosedependent of side effect and improve patient compliance.

• Journal of Ginseng Research
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• 제37권1호
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• pp.135-141
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• 2013

A rapid, sensitive and selective analytical method was developed and validated for the determination of compound K, a major intestinal bacterial metabolite of ginsenosides in human plasma. Liquid-liquid extraction was used for sample preparation and analysis, followed by liquid chromatography tandem spectrometric analysis and an electrospray-ionization interface. Compound K was analyzed on a Phenomenex Luna C18 column ($100{\times}2.00$ mm, 3 ${\mu}m$) with the mobile phase run isocratically with 10 mM ammonium acetate-methanol-acetonitrile (5:47.5:47.5, v/v/v) at a flow rate of 0.5 mL/min. The method was validated for accuracy (relative error <12.63%), precision (coefficient of variation <9.14%), linearity, and recovery. The assay was linear over the entire range of calibration standards i.e., a concentration range of 1 ng/mL to 1,000 ng/mL ($r^2$ >0.9968). The recoveries of compound K after liquid-liquid extraction at 1, 2, 400, and 800 ng/mL were $106.00{\pm}0.08%$, $103.50{\pm}0.19%$, $111.45{\pm}5.21%$, and $89.62{\pm}34.46%$ for intra-day and $85.40{\pm}0.08%$, $94.50{\pm}0.09%$, $112.50{\pm}5.21%$, and $95.87{\pm}34.46%$ for inter-day, respectively. The lower limit of quantification of the analytical method of compound K was 1 ng/mL in human plasma. The developed method was successfully applied to a pharmacokinetic study of compound K after oral administration in ten of healthy human subjects.

• 대한방사성의약품학회지
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• 제2권2호
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• pp.118-122
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• 2016

Integrin ${\alpha}_v{\beta}_3$ plays an important role in the tumor metastases and angiogenesis. Arginine-glycine-aspartate (RGD) peptide motif binds to the integrin ${\alpha}_v{\beta}_3$. General $^{68}Ga$-labeled cyclic RGD peptides was rapidly eliminated from the circulatory system by renal excretion because of its hydrophilic property. The purpose of this study was to develop a novel $^{68}Ga$-labeled cyclic RGD peptides, which could acquire enhanced PET tumor images with improved pharmacokinetics by adopting biphenyl group between chelator and RGD peptides. $^{68}Ga$-DOTA-2P-c(RGDyK) was demonstrated a 12% higher lipophilicity level than $^{68}Ga$-DOTA-c(RGDyK) as a reference compound. In the animal PET, $^{68}Ga$-DOTA-2P-c(RGDyK) represented relatively lower blood-clearance, and an increased signal to noise ratio compared to $^{68}Ga$-DOTA-c(RGDyK). From these perspective, $^{68}Ga$-DOTA-2P-c(RGDyK) could be a good candidate for in integrin ${\alpha}_v{\beta}_3$-expressed tumor imaging.

• 한국임상약학회지
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• 제13권1호
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• pp.1-4
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• 2003

Cyclosporine (CsA) has become well established as a potent immunosuppressive agent in the renal transplantation. However, therapy is complicated by large intraindividual and interindividual variability in pharmacokinetics of CsA and frequent undesirable clinical outcomes such as graft rejection and nephrotoxicity. The objective of this study was to determine the CsA trough blood concentrations that were associated with acute graft rejection and renal toxicity in renal transplant patients. Also, the ability of the current recommendation of therapeutic range for CsA to prevent graft rejections and CsA-associated renal toxicity was assessed. The clinical courses of the patients on CsA as an immusuppressive agent for preventing the graft rejection with renal ransplantation performed at Seoul National University Hospital from January 1995 to September 1998 were retrospectively reviewed. Total of 78 patients were included and three of them were retransplantation cases. Twenty-two acute episodes of rejection were identified, but only 16 episodes were clinically significant. Of these all the episodes occurred during the first month after transplantation except one. Mean daily doses of CsA were $427.2\pm72.1,\;352.6\pm56.8,\;308.62\pm48.3\;and\;268.47.1\;mg$ at posttransplant 1, 3, 6, and 12 months, respectively. Mean CsA whole blood though levels were $259.8\pm36.2,\;238.5\pm39,\;200.8\pm45.8\;and\;161.9\pm25.8\;ng/ml$ at posttransplant 1, 3, 6 and 12 months, respectively. Mean daily doses/weight were $7.9\pm1,\;6.4\pm1,\;5.3\pm0.7\;and\;4.6\pm0.7\;mg/kg$ at posttransplant 1, 3, 6 and 12 months, respectively. CsA doses decreased significantly as months progressed (p<0.001). During the first month after transplantation, only $12.5\%$ of the patients in rejection group had CsA concentration in therapeutic range, and 87.5, 93.8, and $100\%$ were within the therapeutic range at posttransplant 3, 6, and 12 months, respectively. These results suggested that CsA concentrations of $250\sim300\;ng/ml$ might be appropriate for preventing the acute rejection during the first posttransplant month.

• 한국임상약학회지
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• 제22권3호
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• pp.220-227
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• 2012

Kidney and liver are the major organs of metabolism and excretion of drugs. Renal and Hepatic impairment may affect the pharmacokinetics/pharmacodynamics and the safety of drugs. Adjusting the dosage based on organ function is the essential role of pharmacists. However, differences have been noted on the recommended dosage among the literatures. We compared and analyzed the recommendations of 4 literature sources which are commonly used for dosage adjustment. From April, 2011 to August, 2011, we selected data on recommendations for dosage adjustment for impaired renal and hepatic function of 100 drugs through a protocol. We analyzed the definition terms of renal and hepatic impairment, recommendations for dosage adjustment, evidenced references in four literature sources: Korean National Formulary (KNF), American Hospital Formulary System Drug Information (AHFS), Micromedex (MM) and Drug Prescribing of Renal Failure (DPRF). We further examined the data homogeneity by comparing how drugs that required no adjustment according to one source were categorized by the other. Sources use different definition terms among themselves except DRPF. Presence or absence of evidenced references about renal/hepatic functional states are KNF (0%/0%), AHFS (78%/62.6%), MM (87.5%/65.6%) and DPRF (93.2%/no recommendation) respectively. Recommendations of specific dosage and dosing interval are KNF (24%/13%), AHFS (39.6%/12.1%), MM (50%/17.7%), and DPRF (55.4%/no recommendation) respectively. Regarding the data homogeneity, the differences were remarkable. Drugs with no adjustment according to AHFS were categorized to be adjusted/ contraindicated by KNF, MM, DPRF and the values were (44%/5.6%), (22%/0%), and (36%/0%) in renal function, (39%/6.5%), (19%/3.2%), and (no recommendation/no recommendation) in hepatic function respectively. Our study shows remarkable definite variation in definitions and recommendations about definition terms, information of dosage and interval, presence or absence of evidenced references. Especially for KNF, quantitative recommendations on dosages and dosing intervals should be made in the near future. To maximize the drug effect and safety and to minimize the heterogeneity of the literature sources, reviewing at least two sources are suggested when recommending the proper dosage adjustment based on organ function.

• 공업화학
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• 제24권5호
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• pp.443-455
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• 2013

혼합되지 않는 두 용액 사이의 계면(interface between two immiscible electrolyte solutions, ITIES)에서의 전하 이동 반응에 대한 전기화학적 연구는 이온 검출용 센서, 바이오센서, 생체막 모델링, 약물 전달 반응, 상전이 촉매반응, 연료 생성, 태양에너지 전환 등을 포함한 다양한 연구 분야에 적용이 가능하기 때문에 크게 주목받고 있다. 특히 ITIES에서의 이온 전이 반응을 이용하여 이온물질 및 생물질 등을 검출할 수 있는 센서로 개발하기 위해 불안정한 ITIES의 한 쪽 액체층을 젤(gel)화하여 안정화하고, 마이크로 계면 형성을 통해 전압강하를 최소화 시키는 등의 연구가 활발하게 이루어졌다. 본 총설에서는 ITIES 계면에서의 이온 전이 반응을 이용하여 개발된 다양한 센서의 원리와 응용 및 발전 가능성에 대해 다루고자 한다. ITIES 계면을 (i) 보편적인 액체/액체 계면형, (ii) 마이크로피펫 팁형, (iii) 고분자 박막에 형성된 단일 마이크로홀 또는 마이크로홀 어래이형 및 (iv) 실리콘 기판에 제작된 마이크로홀 어래이형으로 분류하고, 이들 계면에서의 직접적인 이온 전이 반응과 보조 이온 전이 반응을 활용하여 수질 환경 오염의 원인이 되는 이온 및 농약 성분을 선택적으로 검출할 수 있는 이온 선택성 센서와 생물질을 분석할 수 있는 바이오센서 개발 연구에 대해 초점을 두고 소개하려 한다.

• 공업화학
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• 제29권5호
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• pp.581-588
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• 2018

본 논문은 편극화된 물/1,2-dichloroethane (1,2-DCE) 계면에서 세포티암(cefotiam, CTM) 항생제 약물의 전이 반응을 전기화학적 방법으로 조사하였다. CTM 약물은 물의 pH에 따라 서로 다른 전하를 가지고 이온화되며 각 pH에서 이들 이온의 전이 반응을 연구함으로써 처음으로 CTM 약물이 좀 더 우세하게 물 또는 유기층에 분배되는 정도를 나타내는 상 분배 도표를 세웠다. 이를 바탕으로 CTM 약물의 형식 전이 전위값 및 형식 Gibbs 전이 에너지 값을 포함한 열역학적 정보와 함께 분배 계수를 포함한 중요한 약물동태학 정보를 얻었다. 특히 pH 3.0 수용액에서 양전하를 띠는 CTM 이온의 전이 반응을 순환전압전류법으로 조사한 결과 CTM 농도에 따라 측정한 전류 값이 비례하여 증가한다는 점을 확인하였다. 이를 바탕으로 CTM 이온을 정량 분석 가능한 센서를 개발하였다. 휴대성과 이동성을 보완하기 위해 polyethylene terephthalate 필름에 마이크로홀을 만들어 지지체로 사용하고, 1,2-DCE 유기용매를 polyvinylchloride-2-nitrophenyloctylether (PVC-NPOE) 유기성 젤로 대체하여 도포하는 방식으로 센서를 제작하였다. 상기 센서를 이용하여 CTM 약물을 $1{\mu}M$에서 $10{\mu}M$까지 정량 분석할 수 있었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.70-81
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• 2000

DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in