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Role of metabolism by intestinal microbiota in oral baicalin pharmacokinetics
정태천 ( Tae Cheon Jeong ) 전남대학교 약품개발연구소 2016 약품개발연구지 Vol.25 No.-
Baicalin (baicalein-7-glucuronide) is a flavonoid purified from Scutellaria baicalensis Georgi that has traditionally been used for treatment of hypertension, cardiovascular diseases, and viral hepatitis. In this study, the effects of intestinal microbiota on the pharmacokinetics of baicalin were investigated in normal and antibiotic-pretreated rats following p.o administration of 100 mg/kg baicalin by using liquid chromatography/ion trap mass spectrometry. When rats were pretreated orally with cefadroxil, oxytetracycline and erythromycin for 3 days to control the number of intestinal bacteria, the pharmacokinetic parameters of oral baicalin were significantly affected by antibiotics: C<sub>max</sub>, T<sub>1/2</sub>, K<sub>el</sub> and AUC values were significantly changed when compared to those in normal rats. These results indicate that intestinal microbiota might play a key role in the oral pharmacokinetics of baicalin.
기니픽을 이용한 BR92021 ( 정제 브이아이 장티푸스 백신 ) 의 항원성 평가
정태천(Tae Cheon Jeong),김갑호(Kap Ho Kim),배주현(Ju Hyun Bae),구희경(Hee Kyoung Gu),서정은(Jeong Eun Suh),박종일(Jong Il Park),차신우(Shin Woo Cha),임상민(Sang Min Lim),정한선(Hahn Sun Jung),김상린(Sang Lin Kim) 한국응용약물학회 1999 Biomolecules & Therapeutics(구 응용약물학회지) Vol.7 No.3
To study the antigenicity of BR92021(Vi polysaccharide typhoid vaccine), active systemic anaphylaxis and passive cutaneous anaphylaxis were tested in guinea pigs. The groups were as follows: group I(low dose, 30 ㎕/kg), group II(high dose, 300 ㎕/kg), group III(300 ㎕/kg plus complete Freund`s adjuvant), group IV(positive control, ovalbumin plus complete Freund`s adjuvant) and group V(saline-treated control). Male Hartley guinea pigs at 7 weeks of age were sensitized subcutaneously with the test article or saline three times per week for three weeks(i.e., total 9 times). For groups III and IV, animals were sensitized subcutaneously with either the test article or ovalbumin plus complete Freund`s adjuvant once per three week for 6 weeks(i.e., total 3 times). Twelve days after the last sensitization, the blood was collected from the sensitized animals for the passive cutaneous anaphylaxis test. In addition, the sensitized animals were subjected to the active systemic anaphylaxis test on fourteen days after the 1st sensitization by an intravenous challenge with either the test article or ovalbumin. In group I, mild(1/5) or moderate(4/5) symptoms of anaphylactic shock were observed. In group II, no sign(1/5), moderate(3/5) and severe(1/5) symptoms were observed. In group III, four animals of 5 revealed moderate signs and one of 5 showed no signs of anaphylactic shock. In group IV, all 5 animals showed severe signs of shock. In group V, one of 5 revealed moderate and four of 5 showed no signs. The necropsy findings related to the active systemic anaphylaxis were observed in most animals of groups I to V. In the passive cutaneous anaphylaxis test, the antiserum was diluted 10- to 5120- fold and was injected intradermally on the clipped back of recipient animals, followed by an intravenous challenge with either the test article or ovalbumin. No animals in groups I, II, III and V showed the positive reaction, whereas all animals in group IV, the positive control, showed the positive reaction at the dilution range of x1280 to x5120. Our results indicate that the test article, BR92021, may have weak antigenic potential in male guinea pigs.
Anthracycline 계 항암성 항생물질 DA-125 의 Beagle dog 에 대한 26 주 반복정맥투여독성시험
정태천(Tae Cheon Jeong),한상섭(Sang Seop Han),양중익(Jung Ick Yang),차신우(Shin Woo Cha),하창수(Chang Su Ha),노정구(Jung Koo Roh),박종일(Jong Il Park),신호철(Ho Chul Shin),김형진(Hyoung Chin Kim) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.2
This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 ㎎/㎏/day, 6 days/week for 26 weeks. At 0.6 ㎎/㎏, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 ㎎/㎏, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 0.6 ㎎/㎏. At 0.0375, 0.15 and 0.6 ㎎/㎏, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 ㎎/㎏ were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 ㎎/㎏, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 ㎎/㎏, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy. Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various lymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 ㎎/㎏. At 0.15 ㎎/㎏, testis was a target organ, while at 0.6 ㎎/㎏ hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 ㎎/㎏ the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.
Cyclophosphamide 의 면역독성 검출을 위한 in vitro 시험법의 개발
정태천(Tae Cheon Jeong),(Michael P . Holsapple),차신우(Shin Woo Cha),하창수(Chang Su Ha),한상섭(Sang Seop Han),노정구(Jung Koo Rho) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.3
A splenocyte culture system supplemented with liver microsomes was developed to detect immunotoxic chemicals which require metabolic activation using cyclophosphamide as a positive standard. When liver microsomes were added to splenocyte cultures isolated from female B6C3F1 mice, the proliferation of splenocytes by lipopolysaccharide (LPS) was increased and the proliferation by concanavalin A (Con A) was decreased. However, when compared with each corresponding control, cyclophophamide was successfully activated to metabolites capable of suppressing lymphoproliferative responses. This suppression was clearly dependent upon the amounts of microsomes added and/or the concentration of cyclophosphamide exposed. In these cultures, the proliferation of splenocytes was suppressed when the cells were exposed to cyclophosphamide on the day of culture initiation. On the other hand, microsome was responsible for the increase in LPS mitogenicity and NADPH was responsible for the decrease in Con A mitogenicity. Finally, our present culture system was compared with the hepatocyte-splenocyte coculture system which we had developed earlier. We found that the hepatocyte-splenocyte coculture was better able to activate cyclophosphamide to metabolites capable of suppressing the antibody response to sheep erythrocytes. Although our present culture system was relatively poor to activate cyclophosphamide in cultures for antibody response, it will be useful as a simple screening method to detect suppression of certain in vitro immunotoxic parameters like LPS mitogenicity by chemicals which require metabolism.