• Parasites, Hosts and Diseases
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• 제60권1호
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• pp.39-43
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• 2022

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 1995년도 정기총회 및 추계학술대회
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• pp.35-35
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• 1995

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2006년도 제15차 추계학술대회
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• pp.86-86
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• 2006

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2005년도 추계학술대회
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• pp.5-9
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• 2005

• 대한한의학방제학회지
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• 제29권4호
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• pp.277-283
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• 2021

Objectives : We investigated the effects of Bojungikgi-tang (BJIGT) on P450 cytochrome enzyme and oxidative stress in the cells. Methods : We enrolled the HepG2 hepatocyte cell line to assess MTT assay, flow cytometer, and immunoblotting analysis. Expression of CYP450 was confirmed by immunoblotting analysis in the Huh7 cell line. Results : We determined that BJIKT markdely changed the expression of the CYP2C19, CYP2D6, and CYP2E1. Moreover, BJIKT inhibited the cell toxicity induced by arachidonic acid + iron treatment, as assessed by FACS analysis. BJIKT induced AMPK activation, which increased the phophorylation of ACC. Conclusions : This study verified the effects of BJIKT, on P450, ROS production, mitochondrial damage and AMPK signaling pathway, which might give us the scientific information about the traditional herbal prescription.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.194-199
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• 2002

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 1998년도 제50차 추계 학술대회 연제집
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• pp.287-288
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• 1998

• Clinical and Experimental Pediatrics
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• 제48권4호
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• pp.380-386
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• 2005

목 적 : 신생아 황달은 백인에 비해 중국, 일본, 한국 등 동아시아인에서 2배 이상 많이 발생하는 것으로 보아 유전적 연관성이 있을 것으로 생각되어 왔고, 최근 일본인, 타이완 중국인, 한국인에서 UGT1A1 유전자의 Gly71Arg 다형성이 신생아 황달과 연관성이 있다고 보고되었다. 선천적으로 UDP-glucuronosyltransferase(UDPGT)에 결함이 있는 경우에는 부경로(alternative pathway)로 CYP1A2 효소를 자극하여 빌리루빈 대사가 이루어진다. 출생 후 6-14주가 되어야 성인 UDPGT 정상치에 도달하기 때문에 신생아 황달에서 빌리루빈 대사에 CYP1A2 부경로가 중요한 역할을 할 것으로 생각된다. 이에 저자들은 UGT1A1과 CYP1A2 유전자의 다형성이 한국인 신생아 황달의 발생과 어떤 연관성이 있는지 알아보고자 본 연구를 시행하였다. 방 법 : 혈중 빌리루빈 수치가 12 mg/dL 이상의 건강하고, 황달의 다른 위험인자가 없는 만삭아 79명과 대조군 68명으로부터 혈액 0.5 cc를 채취하여 DNA을 분리하였다. UGT1A1 유전자는 Polymerase chain reaction(PCR) 후에 염기서열 분석을 통해서 Gly71Arg 유전자 다형성을 확인하였으며, CYP1A2는 제한효소인 MboII를 이용하여 PCR-restriction fragment length polymorphism 방법과 염기서열 분석을 통해서 T2698G 유전자 다형성을 확인하였다. 결 과 : UGT1A1 유전자의 Gly71Arg 다형성은 변이형 대립 유전자 분포가 환자군에서 32%로 대조군 11%보다 높았다(P<0.0001). CYP1A2 유전자의 다형성은 변이형 유전형 분포가 환자군에서는 41.8%, 대조군에서 32.3%로 환자군이 높았으며 통계학적으로 유의하였다(P=0.015). 변이형 대립유전자의 빈도는 환자군에서 21%로 대조군 19%보다 높았으나 통계학적 유의성은 없었다(P=0.706). Gly71Arg와 T2698G의 변이형 발생의 연관성은 없었다(P=0.635). 결 론 : 한국인의 신생아 황달에서 체내의 빌리루빈 대사의 주경로와 부경로에 작용하는 효소의 유전자인 UGT1A1과 CYP1A2의 다형성이 확인되었고, UGT1A1 유전자의 Gly71Arg 다형성은 신생아 황달과 연관이 있었으나 CYP1A2 유전자의 T2698G 다형성은 신생아의 황달과 연관이 없었다.

• Mass Spectrometry Letters
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• 제9권3호
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• pp.86-90
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• 2018

Methallylescaline, 2-(3,5-dimethoxy-4-[(2-methylprop-2-en-1-yl)oxy]phenyl)ethanamine, is a new psychoactive substance with potent agonist of 5-HT receptor, but there is little information on its pharmacological effect, metabolism, and toxicity. It is necessary to characterize the metabolic profiling of methallylescaline in human hepatocytes using liquid chromatography-high resolution mass spectrometry. Methallylescaline was metabolized to three hydroxy-methallylescaline (M1-M3) and dihydroxy-methallylescaline (M4) via hydroxylation in human hepatocytes. CYP2D6, CYP2J2, CYP1A2, and CYP3A4 enzymes were responsible for the metabolism of methallylescaline. The metabolites as well as methallylescaline would be used for monitoring the abuse of methallylescaline.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2002년도 제11차 추계학술대회
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• pp.8-8
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• 2002