대한임상약리학회지에 게재된 논문의 분석

임영채,Lim, Young-Chai 대한임상약리학회 2012 臨床藥理學會誌 Vol.20 No.1

Background: To grasp the status and future directions, an analysis was done on the articles published in the Journal of Korean Society for Clinical Pharmacology and Therapeutics during recent 19 years. Methods: All the articles published from 1993 through 2011 were retrospectively analyzed. The number of articles and their language distribution were assessed. The articles were classified according to research types. Authors' affiliations and research fields of articles were also analyzed. Results: The Journal of Korean Society for Clinical Pharmacology and Therapeutics as a semi-annual journal published 353 articles (3,659 pages in total) since its first issue in May 1993. A total of 37 issues were published with the average of 10.1 articles per issue. Most articles were written in the Korean language (94.9%). In publication type of articles, 13.2% were review articles, 66.7% original articles, 18.0% symposium articles, and the rest other types. In affiliation analysis, most authors were from the academia (91.0%), next from the industry (5.8%), and thirdly from the authority (2.3%). The research field dealt with the highest (28.0%) was Pharmockinetics/Pharmacodynamics/Pharmacometrics (PPP), core of clinical pharmacology. Many articles in PPP field contained the randomized controlled prospective clinical trials, which are the highest level of evidence, indicating high quality of articles. Conclusion: These results suggest that the Journal of Korean Society for Clinical Pharmacology and Therapeutics reflects typically the specialized journal for clinical pharmacology. The internationalization efforts for our journal is also required.

Effects of Intracerebroventricular TFMPP on Rabbit Renal Function

임영채,최종범,김경근,국영종,Lim, Young-Chai,Choi, Johng-Bom,Kim, Kyung-Keun,Kook, Young-Johng The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.2

신장기능조절에 있어서 중추 tryptamine계가 관련되어 있으며, $5-HT_1$수용체는 이뇨적인 역할을 하고 있는 반면에 $5-HT_2$ 및 $5-HT_3$수용체는 항이뇨적인 영향을 미치고 있음이 밝혀진 바 있다. 또한 $5-HT_1$수용체도 단일하지 않고 여러 subtype가 존재함이 알려져 있다. $5-HT_{1A}$수용체의 역할에 관해서는 신기능에 이뇨적인 영향을 미치고 있음이 시사된 바 있다. 본 연구에서는 중추 tryptamine성 신기능 조절에 있어서 $5-HT_{1B}$수용체의 역할을 구명하고자 하였다. 선택적 $5-HT_{1B}$ agonist인 TFMPP $8{\sim}750\;{\mu}g/kg$을 가토 측뇌실내로 투여하면 투여량에 비례하여 이뇨 및 Na과 K 배설의 증가를 초래하였으며, $250\;{\mu}g/kg$ 투여시에는 Na의 배설 분획이 5.44%까지 증가하였다. Na배설 촉진작용은 신혈류역학의 증가 보다도 훨씬 지속하여, 세뇨관에서의 Na재흡수 감소작용이 체액성 기전임을 시사하였다. TFMPP $250\;{\mu}g/kg$ icv투여시에 natriuresis와 함께 혈장내 atrial natriuretic peptide 농도가 약 6배 증가되었다. TFMPP $250\;{\mu}g/kg$을 정맥내로 투여하였을때는 뇌실내 투여시와는 상이하게 신기능에 별다른 유의한 변동을 초래하지 않았다. 이와같은 TFMPP의 diuresis 및 natriuresis는 각각 $5-HT_2$ 및 $5-HT_3$ 수용체의 선택적 antagonist인 ketanserin과 MDL 72222의 전처치에 의하여 차단되지 않았으며, methysergide에 의해서도 억제되지 않았다. 또한 $5-HT_{1A}$ antagonist로 알려진 NAN-190도 TFMPP의 작용을 차단하지 못하였으며 S(-)-propranolol도 영향을 미치지 않았다. 본 연구의 결과 중추 $5-HT_{1B}$수용체는 신장기능에 이뇨 및 Na배설 촉진적인 영향을 미치고 있고 이작용에 atrial natriuretic peptide가 관여함을 알 수 있었다. The central tryptaminergic system has been shown to play an important role in the regulation of renal function: $5-HT_1$ receptor mediate diuresis and natriuresis, whereas both $5-HT_2$ and $5-HT_3$ mediate antidiuresis and antinatriuresis. Recently, $5-HT_1$ receptors are further subdivided into many subtypes, and central $5-HT_{1A}$ subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of $5-HT_{1B}$ subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective $5-HT_{1B}$ agonist in doses ranging from 8 to $750\;{\mu}g/kg$ icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with $250\;{\mu}g/kg$ icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective $5-HT_1$ blocker. Both ketanserin and MDL 72222, selective $5-HT_2$ and $5-HT_3$ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, $5-HT_{1A}$ blocker, affect the TFMPP effects. These observations suggest that central $5-HT_{1B}$ receptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.

중추내로 투여한 5-HT<SUB>1A</SUB> 작동제에 의한 마취 가토에 있어서 신장기능의 변동

임영채(Young Chai Lim),김경심(Kyung Shim Kim),국영종(Young Johng Kook),고정태(Jeong Tae Koh) 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.3

<P> Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT<SUB>1</SUB>(5-hydroxytryptamine<SUB>1</SUB>) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT<SUB>2</SUB> and 5-HT<SUB>3</SUB> receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT<SUB>1A</SUB> subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP(p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT<SUB>1A</SUB> receptors. PAPP in doses ranging from 40 to 350 ㄍg/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption(T<SUP>c</SUP>H<SUB>2</SUB>O), a measure of ADH(antidiuretic hormone) secretion, was increased also. Intravenous 350 ㄍg/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT<SUB>2</SUB> antagonist, 40 ㄍg/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT<SUB>1</SUB> antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT<SUB>1A</SUB> antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT<SUB>1A</SUB> receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.

위약효과로 바라본 의학의 새로운 모습

임영채 ( Lim Young Chai ) 전북대학교 인문학연구소 2020 건지인문학 Vol.0 No.27

Despite the remarkable achievements in treating diseases, modern medicine, based upon the scientific and predictable biomedical paradigm with biological model of disease as the center, has lots of problems including dehumanization of medical practice. Placebo effects, beneficial therapeutic effects happened even in the absence of effective therapeutic substances, could not be explained by the biomedical paradigm of modern medicine. However, many meanings of placebo effects suggest the useful possibilities for improving the problems not solved by existing biomedical model. This study first described many problems of modern medicine, and then discussed new facets of modern medicine contemplated through various meanings of placebo effects in order to improve the problems of modern medicine. What the meanings of placebo effects indicate might be not just to look at medicine in a confined way, which is the case of modern medicine, but to look at medicine more broadly. That is, placebo effects request the expansion to the medicine of our life beyond the science- centered medicine around diseases mainly by medical personnel and institutions, further requiring the comprehensive medicine to consider multi- dimensional factors such as society, environment, ecology, and etc. To this end, placebo effects suggest us to recognize our body not just as the existing biological passive ‘objectified body,’ but as independently connecting relational active ‘lived body.’ Also it requires us to consider the artistic or contextual aspects and connective or shared aspects, which were so far neglected in modern medicine, drawing the fine medicine which is humane and considerate of society and ecology to live with us together.

뇌실내 TFMPP가 가토신장기능에 미치는 효과

임영채(Young Chai Lim),최종범(Johng Bom Choi),김경근(Kyung Keun Kim),국영종(Young Johng Kook) 대한약리학회 1992 대한약리학잡지 Vol.28 No.2

신장기능조절에 있어서 중추 tryptamine계가 관련되어 있으며, 5-HT₁수용체는 이뇨적인 역할을 하고 있는 반면에 5-HT₂ 및 5-HT₃수용체는 항이뇨적인 영향을 미치고 있음이 밝혀진 바 있다. 또한 5-HT₁수용체도 단일하지 않고 여러 subtype가 존재함이 알려져 있다. 5-HT_1A수용체의 역할에 관해서는 신기능에 이뇨적인 영향을 미치고 있음이 시사된 바 있다. 본 연구에서는 중추 tryptamine성 신기능 조절에 있어서 5-HT_1B수용체의 역할을 구명하고자 하였다. 선택적 5-HT_1B agonist인 TFMPP 8 ~ 750μg/kg을 가토 측뇌실내로 투여하면 투여량에 비례하여 이뇨 및 Na과 K 배설의 증가를 초래하였으며, 250μg/kg 투여시에는 Na의 배설 분획이 5.44%까지 증가하였다. Na배설 촉진작용은 신혈류역학의 증가 보다도 훨씬 지속하여, 세뇨관에서의 Na재흡수 감소작용이 체액성 기전임을 시사하였다. TFMPP 250μg/kg icv투여시에 natriuresis와 함께 혈장내 atrial natriuretic peptide 농도가 약 6배 증가되었다. TFMPP 250μg/kg을 정맥내로 투여하였을때는 뇌실내 투여시와는 상이하게 신기능에 별다른 유의한 변동을 초래하지 않았다. 이와같은 TFMPP의 diuresis 및 natriuresis는 각각 5-HT₂ 및 5-HT₃ 수용체의 선택적 antagonist인 ketanserin과 MDL 72222의 전처치에 의하여 차단되지 않았으며, methysergide에 의해서도 억제되지 않았다. 또한 5-HT_1A antagonist로 알려진 NAN-190도 TFMPP의 작용을 차단하지 못하였으며 S(-)-propranolol도 영향을 미치지 않았다. 본 연구의 결과 중추 5-HT_1B수용체는 신장기능에 이뇨 및 Na배설 촉진적인 영향을 미치고 있고 이작용에 atrial natriuretic peptide가 관여함을 알 수 있었다. The central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT₁ receptor mediate diuresis and natriuresis, whereas both 5-HT₂ and 5-HT₃ mediate antidiuresis and antinatriuresis. Recently, 5-HT₁ receptors are further subdivided into many subtypes, and central 5-HT_1A subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of 5-HT_1B subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective 5-HT_1B agonist in doses ranging from 8 to 750μg/kg icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with 250μg/kg icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective 5-HT₁ blocker. Both ketanserin and MDL 72222, selective 5-HT₂ and 5-HT₃ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, 5-HT_1A blocker, affect the TFMPP effects. These observations suggest that central 5-HT_1Breceptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.

적정약물요법을 위한 TDM의 임상적 응용

윤영란,임영채,Yoon, Young-Ran,Lim, Young-Chai 대한임상약리학회 2000 臨床藥理學會誌 Vol.8 No.1

Therapeutic drug monitoring (TDM) among various fields of clinical pharmacology plays the vital role in order to achieve the indivisualization of optimal drug therapy, which is the process of maximizing therapeutic effects and minimizing side effecs, simultaneously. Variable drug responses are largely due to the individual pharmacokinetic variations. Therefore in TDM it is very important to keep optimal drug concentrations, which makes it possible to optimize the clinical outcomes of each patient. In recent, the introduction of clinical pharmacokinetic principles and development of assay methods makes TDM more prevalent. This article describes the clinical significance, functions, and applications of TDM in several aspects. TDM indications, concepts and examples of therapeutic range are also described. The features which should be strived for in each step of TDM process (the decision to request a drug level, blood sampling, laboratory measurement, clinical interpretation of drug concentration, and production of individualized dosage regimen and dosage adjustment) are discussed.

가토신장기능에 미치는 뇌실내 Ketanserin의 영향

국영종(Young Johng Kook),김경근(Kyung Keun Kim),임영채(Young Chai Lim),김유남(Yoo Nam Kim),국훈(Hoon Kook) 대한약리학회 1990 대한약리학잡지 Vol.26 No.2

5-Hydroxytryptamine(5-HT)를 가토뇌실내로 투여 (icv)하면 이뇨와 Na배설증가가 초래되며, 이러한 작용은 5-HT₁ 수용체길항제인 methysergide에 의하여 차단되므로 중추성 신장기능조절에 있어 중추 tryptamine계의 관련이 시사된 바 있다. 본 연구에서는 5-HT₂ 길항제로 알려진 ketanserin (KET)를 이용하여 5-HT₂ 수용체의 역할을 구명하고자 하였다. KET 120μg(=0.3μmoles)/kg icv는 신혈류역학에는 아무런 변동을 일으키지않으나 유의한 Na배설증가를 초래하여, 세뇨관에서의 Na 재흡수 감소가 시사되었다. 전신혈압은 약간 감소하였다. 정맥내 투여시에는 유의한 기능변동을 볼 수 없었다. 5-HT 200μg/kg icv는 경미하나 유의한 Na배설증가 및 이뇨작용을 나타냈다. 그러나 신장기능에 그다지 큰 영향을 미치지 않는 양인 40μg/kg의 KET icv후에는 5-HT의 작용이 크게 강화되어, Na배설분획이 9.3%에 달하였다. Norepinephrine, dopamine, histamine과 같은 다른 생체아민의 신장작용은 KET전처치에 의하여 영향받지 아니하였다. 본 연구는 중추 5-HT₁ 수용체와는 반대로 중추 5-HT₂ 수용체는 항이뇨 및 Na배설감소를 매개하고 있으며, 중추 tryptamine계는 신장기능을 이중적으로 조절하고 있음을 시사하였다. 5-Hydroxytryptamine (5-HT) was reported to elicit natriuresis and diuresis when given intracerebroventricularly (icv) and these effects were shown to be abolished by icv methysergide, 5-HT₁ antagonist, thus suggesting that central tryptaminergic system may also participate in the regulation of renal function. We tried in this study to elucidate the role of 5-HT₂ receptors in the central tryptaminergic regulation of renal function, observing the effects of icv ketanserin, a specific 5-HT₂ antagonist. Ketanserin (KET) icv in doses of 120μg (=0.3μmoles)/kg produced significant natriuresis without affecting renal hemodynamics, indicating that it resulted from decreased tubular Na reabsorption. Systemic blood pressure decreased slightly but significantly. When given iv, no significant effect was observed. 5-HT, 200μg/kg icv, produced mild but significant natriuresis and diuresis. However, after KET, 40μ g/kg icv, a dose which minimally affects renal function, the natriuresis and diuresis by 5-HT was greatly augmented, with the fractional excretion of filtered sodium reaching 9.3%. The renal effects of other biogenic amines administered icv, such as norepinephrine, dopamine and histamine, were not significantly affected by the KET pretreatment. These observations suggest that central tryptaminergic system influences renal function in dual ways, i.e., natriuretic and diuretic influence via 5-HT₁ receptors, whereas 5-HT₂ subtypes mediate the antinatriuretic and antidiuretic effects, and that the central tryptaminergic system plays a role in the regulation of rabbit renal function.

Influence of Intracerebroventricular Ketanserin on Rabbit Renal Function

국영종,김경근,임영채,김유남,국훈,Kook, Young-Johng,Kim, Kyung-Keun,Lim, Young-Chai,Kim, Yoo-Nam,Kook, Hoon The Korean Society of Pharmacology 1990 대한약리학잡지 Vol.26 No.2

5-Hydroxytryptamine(5-HT)를 가토뇌실내로 투여 (icv)하면 이뇨와 Na배설증가가 초래되며, 이러한 작용은 $5-HT_1$ 수용체길항제인 methysergide에 의하여 차단되므로 중추성 신장기능조절에 있어 중추 tryptamine계의 관련이 시사된 바 있다. 본 연구에서는 $5-HT_2$ 길항제로 알려진 ketanserin (KET)를 이용하여 $5-HT_2$ 수용체의 역할을 구명하고자 하였다. KET $120\;{\mu}g(=0.3{\mu}moles)/kg$ icv는 신혈류역학에는 아무런 변동을 일으키지않으나 유의한 Na배설증가를 초래하여, 세뇨관에서의 Na 재흡수 감소가 시사되었다. 전신혈압은 약간 감소하였다. 정맥내 투여시에는 유의한 기능변동을 볼 수 없었다. 5-HT $200{\mu}g/kg$ icv는 경미하나 유의한 Na배설증가 및 이뇨작용을 나타냈다. 그러나 신장기능에 그다지 큰 영향을 미치지 않는 양인 $40{\mu}g/kg$의 KET icv후에는 5-HT의 작용이 크게 강화되어, Na배설분획이 9.3%에 달하였다. Norepinephrine, dopamine, histamine과 같은 다른 생체아민의 신장작용은 KET전처치에 의하여 영향받지 아니하였다. 본 연구는 중추 $5-HT_1$ 수용체와는 반대로 중추 $5-HT_2$ 수용체는 항이뇨 및 Na배설감소를 매개하고 있으며, 중추 tryptamine계는 신장기능을 이중적으로 조절하고 있음을 시사하였다. 5-Hydroxytryptamine (5-HT) was reported to elicit natriuresis and diuresis when given intracerebroventricularly (icv) and these effects were shown to be abolished by icv methysergide, $5-HT{_1}$ antagonist, thus suggesting that central tryptaminergic system may also participate in the regulation of renal function. We tried in this study to elucidate the role of $5-HT_2$ receptors in the central tryptaminergic regulation of renal function, observing the effects of icv ketanserin, a specific $5-HT_2$ antagonist. Ketanserin (KET) icv in doses of $120{\mu}g$ $(=0.3\;{\mu}moles)/kg$ produced significant natriuresis without affecting renal hemodynamics, indicating that it resulted from decreased tubular Na reabsorption. Systemic blood pressure decreased slightly but significantly. When given iv, no significant effect was observed. 5-HT, $200{\mu}g/kg$ icv, produced mild but significant natriuresis and diuresis. However, after KET, $40{\mu}\;g/kg$ icv, a dose which minimally affects renal function, the natriuresis and diuresis by 5-HT was greatly augmented, with the fractional excretion of filtered sodium reaching 9.3%. The renal effects of other biogenic amines administered icv, such as norepinephrine, dopamine and histamine, were not significantly affected by the KET pretreatment. These observations suggest that central tryptaminergic system influences renal function in dual ways, i.e., natriuretic and diuretic influence via $5-HT_1$ receptors, whereas $5-HT_2$ subtypes mediate the antinatriuretic and antidiuretic effects, and that the central tryptaminergic system plays a role in the regulation of rabbit renal function.

생물학적동등성시험을 위한 통계처리 프로그램(BioEquiv)의 개발

윤상후 ( Sang Hoo Yoon ),황난이 ( Nan A Hwang ),임영채 ( Young Chai Lim ),이용복 ( Yong Bok Lee ),박정수 ( Jeong Soo Park ) 한국약제학회 2010 Journal of Pharmaceutical Investigation Vol.40 No.1

임신과 수유기의 적정약물요법

임영채 全南大醫大 2001 전남의대학술지 Vol.37 No.2