α2- 아드레날린 효능제인 UK 14,304 의 이뇨작용에 대한 신장신경 제거의 영향

고석태(Suk Tai Ko),나한광(Han Kwang Na) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.4

This study was performed in order to investigate the effect of renal denervation on diuretic action of UK 14,304, α₂-Adrenergic Agonist, administered into the vein and the carotid artery in dog. The diuretic action of UK 14,304 administered into the vein or the carotid artery was reversed to the antidiuretic action by renal denervation, this time, the decrease of Na^+ excretion amounts in urine (E_(Na)) and the increase of Na^+ reabsorption rates in renal tubule (R_(Na)) were exhibited. This results suggest that central diuretic action of UK 14,304 is mediated by renal nerves and the antidiuretic action of UK 14,304 in denervation kidney is caused by the increase of Na^+ reabsorption rates (R_(Na)) in renal tubules in dog.

클로르프로마진의 클로르프로마진 설폭시드로의 대사동태

정숙진(Sug Jin Jeong),나한광(Han Kwang Na),이용복(Yong Bok Lee) 한국약제학회 1998 Journal of Pharmaceutical Investigation Vol.28 No.4

N/A In order to elucidate the fraction of sulfoxidation in the over all in vivo metabolism of chlorpromazine (CPZ), the sulfoxidation of CPZ to chlorpromazine sulfoxide (CPZSO) was studied in rats. CPZ (10 ㎎/㎏) and CPZSO (1 ㎎/㎏) were injected into the rat femoral vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of CPZ and CPZSO determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the total excreted amounts of CPZ and CPZSO via urinary and biliary route were lower than 1.4% and 10.61% of the administered dose, respectively. And also, it was found that the fraction of systemic clearance of CPZ which formed CPZSO (F_(mi)) was 0.115. These results showed that CPZ was sulfoxized by 11.5% in rats and the residue would be metabolized via the other routes.

원격무선측정장치를 이용한 항히스타민제의 심혈관계영향평가

이윤희(Yun Hee Lee),나한광(Han Kwang Na),윤재석(Jae Suk Yun),정수연(Soo Youn Chung),김주일(Joo-Il Kim),최기환(Ki Hwan Choi) 대한약학회 2006 약학회지 Vol.50 No.2

Two Antihistamines, terfenadine and astemizole have been withdrawn from major markets for the reason that these durgs have been reported to induce QT interval prolongation associaed with the onset of Torsades de Pointes (TdP), resulting in a life-theatening ventricular arrhythmia. In this study, we investigated effects of diphenhydramine on electrocardigrans and hemodynamic parameters in conscious telemetered dogs. We validated and defined the sensitivity of the test system by monitoring basal parameters and using positive control substancem terfenadine. Single administration effects were tested during 24 hours for each test drug at dose 1㎎/㎏, 10㎎/㎏, 30㎎/㎏, 100㎎/㎏. We monitored QT, QTc, heart rate, blood pressure and body temperature after administering test drugs. In conscious telemetered dogs, diphenhydramine significantly prolonged QT (6.8% of basal) and (7.8% of basal) at 100㎎/㎏. Other parameters were not affected significantly. These findings suggest that antihistamines could induce inportant clinical relevance for patients taking excessive dosages of conventional antihistamines and those at risk of developing cardiac arrhythmias. Future studies that include other antihistamines and other classes will be necessary to predict the torsadogenic risk of drug in humans.

5-Hydroxytryptamine (5-HT) 이 개의 신장기능에 미치는 영향

고석태(Suk Tai Ko),나한광(Han Kwang Na),최인(In Choe) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.1

5-Hydroxytryptamine(5-HT, serotonin), when given into the vein, produced antidiuretic action accompanied with reduction of glomerular filtration(GFR), renal plasma flow(RPF), osmolar clearance(Cosm) and amounts of sodium or potassium excreted in urine(E_(Na), E_K), with the augmented reabsorption rates of sodium and potassium in renal tubules. 5-HT, when infused into a renal artery, exhibited diuretic action accompanied with the augmented RPF and increased E_(Na), and E_K in only infused kidney. Antidiuretic action of 5-HT infused into the vein was not influenced by ketanserin, 5-HT₂ receptor blockade, given into a renal artery, vein or carotid artery, by methysergide, 5-HT₁ receptor blockade, given into a renal artery, whereas above antidiuretic action was inhibited by methysergide given into vein or carotid artery. Diuretic action of 5-HT infused into a renal artery in only experimental kidney was blocked by ketanserin injected into a renal artery, was not influenced by methysergide administered into a renal artery. Above results suggest that 5-hydroxytryptamine(5-HT) produced the antidiuretic action through central 5-HT₁ receptor and the diuretic action through 5-HT₂ receptor located in renal tubules of kidney.

개의 신장기능에 미치는 메톡시베라파밀의 영향

고석태(Suk Tai Ko),이한구(Han Goo Lee),나한광(Han Kwang Na) 대한약학회 1992 약학회지 Vol.36 No.1

Methoxyverapamil, Ca2+ channel blocker, when given intravenously by means of bolus, produced the transient increase of urine flow, and then methoxyverapamil was infused in this experiments. Methyoxyverapamil, when infused into vein, elicited the increase of urine flow ancampanied with the increased glomeralar filtration rate(GFR), renal plasma flow(RPF), excretion amounts of sodium and potassium in urine(ENa, Ek) and osmolar clearance(Cosm), whereas produced the no change of free water clearance (CH2O) and the reduction of reabsorption rates of sodium and potassium in renal tubules(RNa, Rk). Methoxyverapamil, when infused into a renal artery, exhibited the diuretic action in only infused Kidney, at this time changes of renal function were the same aspect to that of intravenously infused methoxyverapamil. Methoxyverapamil, when infused into a carotid artery, exhibited the decreased urine flow along with the reduction of Cosm, CH2O) and ENa. Above results suggest that methoxyverapamil possess both the diuretic action by direct action in kidney and antidiuretic action through the central function.

$K-BEtest^{\circledR}$, 새로운 생물학적 동등성 시험 통계처리 프로그램의 개발

이영주,최정호,송세흠,서철환,김동섭,박인숙,최기환,나한광,정석재,이민화,심창구,Lee, Young-Joo,Choi, Jung-Ho,Song, Sae-Heum,Seo, Chul-Hwan,Kim, Dong-Sup,Park, In-Sook,Choi, Ki-Hwan,Na, Han-Kwang,Chung, Suk-Jae,Lee, Min-Hwa,Shim, Chang-K 한국약제학회 1998 Journal of Pharmaceutical Investigation Vol.28 No.4

A computer program for personal computers, $K-BEtest^{\circledR}$, was developed to analyze bioequivalence data in accordance with Korean Guidelines for Bioequivalence Test (KGBT). This program is user-friendly, interactive, Hangul-compatible and supports $2{\times}2$ cross-over design as well as $2{\times}2$ Latin square design with various significance levels. This program is able to calculate AUC, $C_{max}$ and $T_{max}$ parameters from the blood drug concentration-time profile of individual subjects and evaluate the parameters statistically for the bioequivalence by ${\pm}20%$ rule, the F-test, the Non-centrality test and 90% confidence intervals. All procedures are supported with graphic interface, interactive menu and outputs in Korean. In this paper, two experimental data sets were analyzed by the program and detailed process was demonstrated. The $K-BEtest^{\circledR}$ program appears to be very effective for analyzing bioequivalence data and can be widely used with convenience and accuracy.

이부프로펜이 씨프로플록사신의 생체이용률에 미치는 영향

박인숙(In Sook Park),최기환(Ki Hwan Choi),나한광(Han Kwang Na),정혜주(Hye Joo Chung) 대한약학회 2000 약학회지 Vol.44 No.6

The effects of ibuprofen on bioavailability of ciprofloxacin were studied in rabbits. Animals were divided into three groups ; group A received 60mg/kg of ciprofloxacin; group B and C received 60mg/kg of ciprofloxacin with 60 and 240mg/kg of ibuprofen, respectively. Ciprofloxacin and ibuprofen were given by single oral administration. Serum concentrations of ciprofloxacin were measured by high performance liquid chromatography with UV detector and pharmacokinetic parameters were calculated. Area under the serum concentrations versus time curve (+/-S.E.) of ciprofloxacin were decreased in group B and C compared with group A (12.26+/-0.94 and 12.57+/-0.94 vs. 15.71+/-1.06mcg.hr/ml, p<0.05), whereas total clearances were increased (1.81+/-0.13 and 1.76+/-0.12 vs. 1.40+/-0.09 l/hr/kg, p<0.05). No significant differences in these parameters were observed between group B and C. Relative bioavailability of group B and C to group A were 78 and 80%, respectively. These results suggest that the coadministration of ibuprofen with ciprofloxacin may reduce the bioavailability of ciprofloxacin.

K-BEtestⓡ , 새로운 생물학적 동등성 시험 통계처리 프로그램의 개발

이영주(Young Joo Lee),최정호(Jung Ho Choi),송세흠(Sae Heum Song),서철환(Chul Hwan Seo),김동섭(Dong Sup Kim),박인숙(In Sook Park),최기환(Ki Hwan Choi),나한광(Han Kwang Na),정석재(Suk Jae Chung),이민화(Min Hwa Lee),심창구(Chang Koo Shi 한국약제학회 1998 Journal of Pharmaceutical Investigation Vol.28 No.4

N/A A computer program for personal computers, K-BEtest^ⓡ, was developed to analyze bioequivalence data in accordance with Korean Guidelines for Bioequivalence Test (KGBT). This program is user-friendly, interactive, Hangul-compatible and supports 2×2 cross-over design as well as 2×2 Latin square design with various significance levels. This program is able to calculate AUC, C_(max) and T_(max) parameters from the blood drug concentration-time profile of individual subjects and evaluate the parameters statistically for the bioequivalence by ±20% rule, the F-test, the Non-centrality test and 90% confidence intervals. All procedures are supported with graphic interface, interactive menu and outputs in Korean. In this paper, two experimental data sets were analyzed by the program and detailed process was demonstrated. The K-BEtest^ⓡ program appears to be very effective for analyzing bioequivalence data and can be widely used with convenience and accuracy.

玉蜀黍毛 水性엑기스의 賢臟作用

羅漢光,李漢九,高錫太 조선대학교 약학연구소 1991 藥學硏究誌 Vol.13 No.1

Stigma Maydis Water Extract (SWE), when given intravenously, produced the diuretic action accompanied with the increased amounts of sodium (E_Na) and potassium (E_K) excreted in urine, and the decreased reabsorption rates of sodium (R_Na) and potassium (R_K) in renal tubules, and then glomerular filtration rate (GFR) and renal plasma flow (RPF) were not changed, osmolar clearance (Cosm) was augmented, but free water clearance (??) was diminished. SWE, when given into a renal artery, or into carotid artery, elicited the decreased urine flow, GFR, RPF, E_Na the unchanged R_Na, E_K and R_K in both kidney. Above results suggest that SWE exhibit the central antidiuretrc action, and diuretic action by inhibition of electrolytes in renal tubules through humoral natriurectic agent.

PBPK(생리학적약동력) 방법을 이용한 화학물질의 체내동태에 관한 연구

김동섭,나한광,박인숙,서수경,최기환,김학림,황인영 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

PBPK model은 물질을 투여한 후 시간에 따른 각 조직내의 농도를 예측하는데 생리학적 인자(체중,조직의 체적,켤류량, 심박동수, 체포순환 둥f, 물질의 분배계수 및 생화학적 상수(분포.율. 대사율, 단백질결합상수 둥)를 사용하는 것으로 이 방법은 고롱도에서 저농도로의 변화에 따른 조직의 농도추정, 투여경로에 따른 농도의 변화 그리고 실험동울을 통하여 얻어진 실험값의 잃체로의 적용에 매우 유용한 방법이다. 또한 여러물질의 약동력 기전에 대한 정보를 규명하기에 용이한 장점이 있어 국태에서도 PBPK model의 확립이 필요하다. 이에 사용빈도it 높은 진통소염제인 케토로락의 모델을 확립 후, 그 if!확성을 밉증하고 향후 이 약물들과 병통하는 타 약물과의 상호작용 예측에 필요한 기초를 화립하고자 하였다. A physiologically-based pharrnacokinetic (PBPK) model for a target chemical baa the tissue dosirRetry and PBPK approach (or the tissue dosimetry has several advantages against data-based mathem,ttical pharmacokinetics. Main issue to build and use a PBPK model is to carry out route-to-route aBd high-to-low dose extrapolations as welt as species extrapolation. Kineticfelg HLtn;naf frnw, #vnDr;mpnlt wrrp f;flpf wifh n nrim iliup PTPf mnApl nnd in vivo kinetic COnEtantsconstants and biochemical parameters calculated from experimental results for estiraating distributionrnt n rhpm irnl iT farrpl liTTllrl Kefnrotnr has been shown to be effective for moderate to severe Pain 『☞lief such as postpartum and postoperative pain. We investigated PBPK modet of ketorolac and thenup PBPK modeling/ACSL si3uulation.