Diclofenac Diethylammonium 플라스터제 (류마스탑${\circledR})$의 경피흡수에 따른 임상약동학적 특성의 분석

윤영란,차인준,손지홍,김경아,김민정,박성욱,서승석,최장석,이형기,신재국,Yoon, Young-Ran,Cha, In-June,Shon, Ji-Hong,Kim, Kyoung-Ah,Kim, Min-Jung,Park, Sung-Wook,Seo, Seung-Seok,Choi, Jang-Seok,Lee, Hyeong-Ki,Shin, Jae-Gook 대한임상약리학회 2000 臨床藥理學會誌 Vol.8 No.1

Background: Transdermal absorption pharmacokinetics of diclofenac diethylammonium(DEA) plaster $(Rheumastop{\circledR})$ were estimated after single and multiple application in normal healthy subjects. Methods : Single plaster of 120 mg diclofenac DEA was applied to upper arm of 14 healthy male subjects for 24 hours and replaced with new plaster every 24 hours for following 14 days. Serial blood samples were drawn after the first dose and the last dose of the plaster and intermittent blood samples were drawn at 3, 5, 7 and 10 days of the study. Diclofenac concentrations in plasma, urine and plaster were determined by high performance liquid chromatography method. Pharmacokinetic parameters were estimated by both noncompartmental analysis and compartmental analysis of 2-compartment, 2-segment simultaneous input model with using $(NONMEM{\circledR})$ Results : The amount of diclofenac absorbed during 24 hour application of each diclofenac DEA plaster was estimated to $6.6{\pm}3.5$ mg and was corresponded to 6.9 % of total amount of diclofenac measured in the in tact plaster(average 95.17 mg). After the first dose of a diclofenac plaster, the average peak plasma concentration was reached to maximum concentration $(7.4{\pm}3.6 ng/ml)$ at $12.4{\pm}9.2$ hour. After multiple doses of diclofenac DEA plaster, the plasma concentration reached to peak level $(15.9{\pm}11.7 ng/ml)$ at $7.9{\pm}7.4$ hours, then concentrations were declined very slowly to $(10.0{\pm}5.1 ng/ml)$ at the time of next application. The mean AUC of diclofenac at steady state was estimated to $273{\pm}205 ng/ml$ h. From the compartmental model for the transdermal absorption of diclofenac DEA plaster, $75{\pm}14$ % of diclofenac dose was described by the burst zero order input model and the remained was by slow first order input model. The estimated volume of distribution (Vd/F) was estimated to $2.2{\pm}0.8$ L/kg and half life was $3.4{\pm}0.8$ hour. Conclusions : The diclofenac DEA plaster which shows initial burst and slow continuous input absorption kinetics appears to be able to maintain constant plasma level during 24 hour application. The measured plasma concentration-time profiles at steady-state are expected to be adequate for therapeutic effect, taking into account the comparable results to those from twice a day application of 185 mg diclofenac HEP plaster of which clinical effect has been well established. However, further clinical trials in patients are remained to document the clinical effects of this new diclofenac plaster.

일측 신절제술 후 Netilmicin의 약동학적 특성의 경시적 변화

민권식,손지홍,차인준,정재일,최성협,신재국,윤영란,Min, Kweon-Sik,Shon, Ji-Hong,Cha, In-June,Jung, Jae-Il,Choi, Sung-Hyup,Shin, Jae-Gook,Yoon, Young-Ran 대한임상약리학회 1999 臨床藥理學會誌 Vol.7 No.1

연구배경: 일측 신절제술 후 이를 보상하기 위하여 남은 일측신장은 형태학적, 기능적인 변화를 나타낸다. 본 연구에서는 일측 신절제에 따른 신기능 변화에 따른 약물소실의 변화를 평가하기 위하여 일측 신절제술을 시행한 환자에서 netilmicin의 약동학적 변화를 수술 후 3개월까지 경시적으로 분석하였다. 방 법: 수술 후 netilmicin을 투여 받는 42명 (27명 : 일측 신절제술, 15명 : 대조군, 신절제술이 아닌 비뇨기과적 수술)의 환자를 대상으로, $2.5{\pm}0.3\;mg/kg$의 netilmicin을 일일 2회 반복투여 후 수술 1일 전, 술 후 1일, 3일, 7일 그리고 술 후 3개월에는 1회 투여 수 각각 2회의 채혈을 실시하였다. 이로부터 측정한 혈장 netilmicin 농도를 PCNONLIN을 이용하여 1-compartment 모델에 적용하여 약동학적 파라메터들을 산출하였다. 결 과: 일측 신절제술 후 혈장 크레아티닌치의 증가가 전 연구 기간에 걸쳐 나타났으며, 크레아티닌 청소율은 전 연구 기간 동안에 술전에 비하여 감소된 것으로 나타났다. 한편, 일측 신절제 후 산출된 netilmic의 최고농도는 술전에 비하여 유의한 변화가 없었으나, 술 후 7일 째의 netilmicin 최저 농도는 술전의 값$(0.41{\pm}0.11\;mg/L)$에 비하여 2배 정도 증가하였고 이는 술 후 3개월에는 술전의 수치로 회복되었다. Netilimicin의 혈장 청소율은 수술 후 점차로 감소하여 술 후 7일 째에 술전에 비하여 $27.4{\pm}5.8%$ 감소하여 가장 큰 변화를 보였다. Netilmicin의 반감기는 연장되었으며 신절제 후 7일에 술전에 비하여 $48.7{\pm}9.5%$ 연장되어 가장 큰 변화를 보였다. 변화한 혈장 청소율과 반감기는 술 후 3개월 째에는 술전의 수치로 회복되었다. 일측 신절제 후 감소한 netilmicin의 청소율의 퍼센트 변화량은 혈장 creatinine 값과 유의한 상관관계를 나타내었으며 (r= 0.05, p<0.01), 크레아티닌 청소율과도 유의한 상관관계를 보였다(r=0.47, p<0.01). 결 론: 이상의 결과들은 정상적인 기능을 하고 있는 일측 신장을 절제할 경우 변화된 신기능으로 인해 약물소실이 수개월간 영향을 받을 수 있으므로 일측 신절제술 직후 주로 신장을 통해 배설되는 약물 혹은 활성 대사 물에 대해서는 주의깊게 관찰해야하며, 약동학적 지식을 이용한 개별화된 적정요법을 적용하는 것이 필수적인 것으로 사료된다. Background : After unilateral nephrectomy, one remained kidney adapts morphologically and functionally in order to compensate the loss of opposite kidney. In this study, pharmacokinetics of netilmicin were repeatedly estimated to evaluate the time course of the renal functional changes on drug excretion after unilateral nephrectomy. Methods : After single or multiple doses of netilmicin$(2.5{\pm}0.3\;mg/kg)$, two blood samples were drawn at 1 day before, 1, 3, 7 days and 3 months after operation in 42 subjects (27 patients with unilateral nephrectomy and 15 control patients with general urological operations). Pharmacokinetic parameters were estimated from nonlinear fittings of plasma netilmicin concentrations to one compartment model with using PCNONLIN. Results : The serum creatinine and creatinine clearance were significantly changed compared to those values before operation and to those of control subjects. Without any significant changes of extrapolated peak netilmicin concentrations, trough concentrations increased up to 2.0 folds of baseline level$(0.41{\pm}0.11mg/L)$ at 7days after unilateral nephrectomy. Total netilmicin clearance was gradually decreased and the plasma half-life was prolonged, and the maximum changes of them were observed at 7days after nephrectomy($27.4{\pm}5.8%\;and\;48.7{\pm}9.5%$ of baseline values $90.1{\pm}5.4\;ml/kg/hr$ and $2.6{\pm}0.2hr$, respectively). All these pharmcokinetic changes of netilmicin were recovered to the baseline value at 3 months. The percent changes of netilmicin clearance showed good correlation with the serum creatinine concentration(r=0.50, p<0.01) and creatinine clearance(r=0.47, p<0.01). Conclusions : These results suggest that the renal function on drug excretion seems to change till months later after unilateral nephrectomy of a functional kidney and the close monitoring of a drug and/or metabolite excreted largely by kidney should consider in the subject with very recent unilateral nephrectomy.

신장이식 환자에서 Rifampin과 Cyclosporine의 약동학적 상호작용

손지홍,윤영란,김경아,박지영,차인준,김양욱,김영훈,신재국,Shon, Ji-Hong,Yoon, Young-Ran,Kim, Kyoung-Ah,Park, Ji-Young,Cha, In-June,Kim, Yang-Wook,Kim, Young-Hoon,Shin, Jae-Gook 대한임상약리학회 2000 臨床藥理學會誌 Vol.8 No.1

Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods : Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using $WinNonlin{\circledR}$ Results : After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from $291.1{\pm}54.1$ ng/ml to $950.7{\pm}174.7$ ng/ml and from $1483.1{\pm}92.0$ ng/ml ${\cdot}$ h to $6047.2{\pm}666.6$ ng /ml ${\cdot}$ hr, respectively (p<O.Ol). Total oral clearance (Cl/F) estimated during administration of rifampin ($19.8{\pm}3.5$ L/kg) was decreased to $6.0{\pm}0.9$ L/kg after withdrawing rifampin. However, the prolongation of halflife was not statistically significant $(6.1{\pm}1.7 hour vs)$ $10.6{\pm}1.1)$. Conclusions : These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.

Ketoprofen 전신투여후 활액내로의 분포 약동학 : 집단약동학적 분석

박지영,손정환,윤영란,손지홍,차인준,서승석,최장석,신재국,Park, Ji-Young,Sohn, Jeong-Hwan,Yoon, Young-Ran,Shon, Ji-Hong,Cha, In-June,Seo, Seung-Suk,Choi, Jang-Suk,Shin, Jae-Gook 대한임상약리학회 2001 臨床藥理學會誌 Vol.9 No.1

Background : The disposition kinetics of ketoprofen into synovial fluid was estimated to predict the time course of ketoprofen concentration in synovial fluid in patients with arthritis. Methods : After repeated oral doses of ketoprofen 100 mg twice daily, ketoprofen concentrations of plasma and synovial fluid were determined at steady-state by high performance liquid chromatography(HPLC) in 17 arthritic patients. Plasma pharmacokinetic parameters were estimated from one compartmental open model and the penetration pharmacokinetic parameters into synovial fluid were estimated from nonlinear fitting to the effect compartment model using $NONMEM^{\circledR}$. Results: At steady-state, the observed peak concentrations of plasma and synovial fluid were $4.6{\pm}3.2{\mu}g/ml\;and\;2.4{\pm}1.9{\mu}g/ml$ at 2 hours and 5 hours after the last dose, respectively. Plots of plasma ketoprofen concentration against synovial concentration showed anticlockwise hysteresis, suggesting the time delay in the distribution of ketoprofen into synovial fluid from plasma. The estimated average rate constant for the ketoprofen loss from synovial $fluid({\kappa}_{co})$ was $0.16\;h^{-1}$. From the simulation of ketoprofen concentration curves, the predicted $C_{max}$ of synovial fluid was corresponded to 76.6 % of the plasma $concentration(1.44\;{\mu}g/ml\;vs\;1.881{\mu}g/ml)$ and time lag of $T_{max}$ between both fluid spaces was estimated to 3.1 hours. Conclusions : These results suggest that the time course of ketoprofen concentration in synovial fluid is different from plasma concentration-time profile after systemic administration of ketoprofen. The effect compartment model approach appears to be useful to predict the kinetics of ketoprofen in synovial fluid from the plasma data.

Studies on Intestinal Trematodes in Korea

Byong-Seol Seo(徐丙卨),In-June Cha(車仁濬),Jong-Yil Chai(蔡鍾一),Sung-Jong Hong(洪性琮),Soon-Hyung Lee(李純炯) 대한기생충학열대의학회 1985 The Korean Journal of Parasitology Vol.23 No.1

한국인의 Cytochrome P450 2C19 유전형 분석

윤영란,이준호,김문경,손지홍,이상섭,김종신,이순용,차인준,신재국,Yoon, Young-Ran,Lee, Jun-Ho,Kim, Moon-Kyung,Shon, Ji-Hong,Lee, Sang-Seop,Kim, Jong-Shin,Lee, Soon-Yong,Cha, In-June,Shin, Jae-Gook 대한임상약리학회 2002 臨床藥理學會誌 Vol.10 No.1

배경 : 간 cytochrome P450 2C19 (CYP2C19) 효소군은 유전적 다형성을 나타내는 대표적인 약물대사효소의 하나로, 본 연구에서는 다수의 한국인에서 CYP2C19 유전자 변이를 분석하고, 이들 변이 allele들의 출현빈도를 타 종족에서의 결과와 비교 분석하였다. 방법 : 282 명의 건강한 한국인 피험자에서 CYP2C19 (*2와 *3) allele 변이를 polymerase chain reaction restriction fragment length polymorphism (PCR­RFLP) 방법을 이용하여 분석하였다. 결 과 : 282명의 한국인 피험자 CYP2C19*1/*1 (41.8%), CYP2C19*1/*2 (35.5%), 및 CYP2C19*1/*3 (8.5%) allele 변이를 가지는 extensive metabolizer(EM)는 총 242명으로 나타났다. 40명 (14.2%)은 CYP2C19 의 poor metabolizer(PM)로 밝혀졌는데, 이들의 allele 빈도는 CYP2C19*2/*2, CYP2C19&2/*3, 및 CYP2C19*3/*3 가 각각 8.9%, 3.9%, 1.4% 로 나타 났다. 또한, 총 564개 allele에서 각 allele의 출현빈도는 CYP2C19*1, CYP2C19*2, 및 CYP2C19*3가 각각 63.8%, 28.6% 및 7.6%로 나타났다. 결 론 : 한국인의 CYP2C19 PM 유전형의 빈도는 중국인, 일본인 등의 동아시아인보다 다소 낮았으나, 이는 서양인에 비해서는 유의하게 높은 것으로 나타났다. Background : The cytochrome P450 2C19 (CYP2C19) is a well known microsomal oxidizing enzyme showing genetic polymorphism. We extensively evaluated the frequency distribution of the CYP2C19 allelic variants in a Korean population and compared to those of other ethnics. Methods : Genotyping of CYP2C19 (*2 and *3) was carried out in a total of 282 unrelated Korean subjects. CYP2C19 genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results : Two hundred forty two of 282 Korean subjects, carried extensive metabolizer(EM) genotypes including CYP2C19*1/*1 (41.8%), CYP2C19*1/*2 (35.5%), and CYP2C19*1/*3 (8.5%), respectively. Forty subjects (14.2%) were identified to have CYP2C19 poor metabolizer(PM) genotype, and the frequencies of CYP2C19*2/*2, CYP2C19&2/*3, and CYP2C19*3/*3 were 8.9%, 3.9%, 1.4% respectively. The allele frequencies of CYP2C19*1, CYP2C19*2, and CYP2C19*3 among 564 alleles evaluated were 63.8%, 28.6% and 7.6%, respectively. Conclusions : These results suggest that frequency of CYP2C19 PM genotypes is slightly lower than that of other East Asians including Chinese and Japanese, but significantly higher than Caucasian.

B(a)P, DMBA 및 DMN의 세포매개성 돌연변이 형성기전에 있어 마우스 Strain차 및 Cytochrome P-450 Isozymes의 역할

차인준 인제대학교 1988 仁濟醫學 Vol.9 No.4

화학적 발암 및 돌연변이 유발물질인 B(a)P, DMBA 및 DMN의 세포매개성 돌연변이 유발작용이 마우스 strain차 및 Cytochrome P-450 isozymes에 의하여 어떤 영향을 받는 지를 실험 관찰하여 보고하는 바이다. The change in mutagenic activities of chemical carcinogens, 7,12-dimethyl benz(a)anthracene(DMBA) benzo(a) pyrene (B(a)P) and N-nitrosodimethylamine (DMN) have been investigated using V79 chinese hamster cells as target cells in non-induced, 3-methylcholanthrene(MC) -induced and phenobarbital (PB) -induced C57 Black, C3H and B6 mice, respectively. The number of 6-thioguanine-resistant mutants showed remarkable dose-dependent increase by treatment of DMBA and B(a) P in every 3-MC-induced mice irrespective of mouse strain. In PB-induced mice, number of the resistant mutants to 6-TG were slightly higher than non-induced group by treatment of DMBA in every strain. On the contrary, compared to the control group, number of the resistant mutants to 6-TG were reduced in the B(a)P-treated groups. DMN had produced 6-thioguanine-resistant mutants proportionately as a function of concentration, but was not affected by 3-MC and PB pretreatment, These results suggest that 3-MC and PB induced the different kinds of cytochrome P-450 isozymes and these isozymes may not be responsible for converting DMN into active mutagenic products.

Selenium 부족 식이가 흰쥐 간장에 미치는 영향

김은희,이현기,양영철,차인준 인제대학교 1990 仁濟醫學 Vol.11 No.3

Se 부족에 의하여 랫트의 체중과 사료 섭취량은 감소되었으며 혈중 LDH, GOT와 간장조직의 glutathion 농도는 정상보다 증가되었다. Se 부족군의 조직학적 소견은 간세포의 공포화 변성, 간조직의 PAS 반응 저하, LDH 활성화 감소 및 ACP 활성의 증가를 나타내었으며, rER의 분절화 현상 및 감소와 mitochondria의 종창 등이 관찰되었다. The objective of this study was to determine the effect of Se-deficient diet on the weight gain, chemical changes in plasma and microstructural change of liver in rat. Rats were divided into 2 diet groups (Se-deficient diet) and control diet and sacrificed after 21days of feeding. Levees of LDB, GOT, GPT of Plasma arid glutathione of liver were determined and light microscopic and electron microscopic observation of ret liver were performed. Total weight gaits (P<0.05) and feed efficiency radio (P<0.001) were significantly lower in Se-deficient group than in control group, whereas the levels of plasma LDH (P<0.001) and GOT (P<0.05) were increased significantly in Se-deficient group. Furthermore, the levels of total glutathione (P<0.01) and reduced glutathione (P<0.001) showed significant increase in Se-deficient group. Light microscopic observations showed that cytoplasmic blooning degeneration and pyknosis of nuclei were often found around portal canal of Se-deficient group by H-E straining. PAS staining also showed weakly positive reaction around central area, whereas PAS negative reacting cells were often observed around portal canal of Se-deficient group. Histochemical staining skewed that cytochrome oxidase activity were very active in both groups, whereas LDH activity was significantly decreased arid ACPase activity was significantly increased in Se-deficient group. Electron microscopic observation showed that the number of rER were decreased and the blooning degeneration of rEr was often observed in Se-deficient group. Mitochondria with mayeline figure arid wooly density were also observed in Se-deficient group. Light microscopic observations showed that cytoplasmic blooming degeneration and pyknosis of nuclei were often found around poral canal of Se-deficient group by H-E staning. PAS staining also showed weakly positive reaction around central area, whereas PAS negative reacting cells were often observed around portal canal of Se-deficient group. Histochemical staining showed that sytochrome oxidase activity were very active in both groups, whereas LDH activity was significantly decreased and ACPase acclivity was significantly increased in Se-deficient group. Electron microscopic observation stewed that the number of rER were decreased and the blooning degeneration of rER was often observed in Se-deficient group. Mitochondria with myeline figure and wooly density were also observed in Se-deficient group.

정신분열병 환자의 우울증에서 Paroxetine과 삼환계 항우울제 병용치료

심주철,공보금,박정환,윤영란,신재국,김정익,안동성,김용관,차인준,김영훈 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.4

저자들은 마산동서병원에 입원중인 우울증이 동반된 정신분열증 환자 10명을 대상으로 사용중인 항정신병약물에 paroxetine과 저용량의 삼환계 항우울제를 6주간 병용투여한 후 우울증상에 대한 효과와 치료의 안전성 및 약물상호작용을 알아보았다. Paroxetine은 고정량의 항정신병약물과 삼환계 항우울제에 부가하여 일일 20㎎을 6주간 병용하게 하였으며, 임상상태는 HDRS, HARS, UKU Side Effect Rating Scale등의 평가척도를 사용하여 평가하였다. 또한 약동학적 약물상호작용은 삼환계 항우울제들의 혈장농도를 HPLC로 측정하여 분석하였다. 결과는 다음과 같다. 1) 10명의 전체 대상환자에서의 HDRS 평균점수는 TCA와 paroxetine 병용투여 6주후에 통계적으로 유의하게 감소되었다. 이중 40%의 환자에서는 병용투여 6주후에 HDRS 점수상 50% 이상의 감소를 보여, 일부의 환자들에서는 정신분열병에 동반된 우울증상의 치료에 소량의 삼환계 항우울제와 paroxetine의 병용치료가 효과가 있음을 확인하였다. 2) 두 명의 환자에게서 심각한 약물독성이 발생하였다. 이중 한 명은 삼환계 항우울제의 높은 혈중농도로 인한 항콜린성 위기(anticholinergic crisis) 소견을 보였으며, 다른 한 명은 인지기능 및 의식수준은 명료하였으나 망상과 환각증상이 약화되는 소견을 보였다. 따라서 본 연구에서 시도된 복합적 약물치료의 경우, 삼환계 항우울제의 혈중농도의 측정을 포함한 세심한 임상적 추적이 필요하다고 생각된다. 3) 기저치의 amitriptyline과 그 대사물인 nortriptyline의 농도합. imipramine과 대사물인 desipramine의 농도합은 각각 47.8-226.5ng/㎖. 80.5-395.6ng/㎖였으며 일반적으로 이들 약물들의 단독사용시에 문헌에 보고된 혈중농도를 훨씬 상회하고 있었다. 이는 병용투여된 항정신병 약물 약시 강력한 CYP2D6 효소억제제로서 기저치의 삼환계 항우울제들의 혈장농도를 이미 상당히 증가시켰던 것으로 판단되며, 그러한 결과로 인해 본 연구에서는 paroxetine이 이전의 문헌보고들과는 달리 뚜렷하게 삼환계 항우울제들의 혈장농도를 증가시키지 못하였다. 본 연구는 SSRI와 삼환계 항우울제의 병합 투여가 우울증의 개선 효과를 빠르게 하고, 치료역을 넓히고, 약물상호작용의 결과 paroxetine이 삼환계 항우울제의 혈중농도를 증가시킨다는 기존의 연구결과를 이용하여 정신분열병 우울증상의 치료에 parotextine과 소량의 삼환계 항우울제를 병용하는 방법을 시도해 본 연구이다. 저자들은 이러한 약물치료가 일부의 환자들에게서 효과가 있음을 관찰하였으나, 항정신병약물과 삼환계 항우울제를 병용투여 할 경우는 물론 이에 paroxetine과 같은 선택적 세로토닌 재흡수 억제제를 병용할 경우 복합약물상호작용의 결과로 약물독성의 위험성이 크며 세심한 주의가 필요함을 경험하였다. Depression is well-known to comorbid with several psychiatric disorders. Many schizophrenics also suffer from depression in the course of their illness. Combined therapy of SSRI and tricyclic antidepressants were reported to have benefits in some depressed patients. Paroxetine, a potent CYP2D6 inhibitor, increases the blood levels of tricyclic antidepressant markedly. Using paroxetine, we tried this combined therapy in the treatment of depressive symptoms in 10 chronic schizophrenic inpatients and evaluated its efficacy and drug interactions between paroxetine and tricyclic antidepressants. The following results were obtained : 1) The mean score of Hamilton's Depression Rating Scale(HDRS) was reduced significantly after 6 weeks-trials of this combined therapy for the mild depressive symptoms in 10 chronic schizophrenics. In four patients, 50% or more reductions in the scores of HDRS were noticed at final evaluation. 2) Two among our 10 subjects experienced severe toxic behavioral problems. Anticholinergic crisis with toxic confusion due to high blood levels of tricyclics was found in one patient and the other showed rapid clinical deterioration in his psychotic symptoms such as delusion and hallucination without any consciousness alternation. 3) Baseline plasma levels of tricyclics before adding paroxetine were higher than expected in our chronic schizophrenic subjects maintained with their antipsychotic medications. Several antipsychotics were also known as a potent CYP2D6 inhibitors and to increase the blood levels of tricyclics. Because the blood levels of tricyclics had already increased significantly by the use of antipsychotics, adding paroxetine to antipsychotics and tricyclic antidepressant in our subjects could increase the blood levels of tricyclics not so much as previously reported in the literatures.

신생아에서 Amikacin의 집단약동학

윤영란,신종범,손지홍,박지영,임은주,김혜리,정원석,김철호,이순용,차인준,신재국 大韓臨床藥理學會 2000 臨床藥理學會誌 Vol.8 No.2