• Toxicological Research
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• 제26권4호
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• pp.275-283
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• 2010

Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.

• 대한수의학회지
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• 제40권4호
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• pp.741-746
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• 2000

최근 새로 개발중인 항AIDS치료제 KR-V 시리즈를 대상으로 HPLC-UV 검출법을 이용해 랫드 혈장중에서 분석법을 검토하였다. 분석컬럼은 $C_{18}$($5{\mu}m$, $250{\times}2.0mm$ I.D.)을 이용하였으며 이동상은 물과 ACN의 혼합액(40/60, v/v)으로 하였다. 이상의 조건에서 모든 KR-V 물질들은 용출시간 4-12분에 비교적 신속하게 잘 분리되었으며 정량한계는 15-30 ng/ml, 혈장중 회수율은 KR-V 2, 7 및 15를 제외하고는 85%(C.V. <10%) 이상으로 나타내었다. Ester 구조를 포함하고 있는 KR-V 2, 7 및 15는 혈장중에서 극히 불안정하여 유도체 개발의 분자설계상 제외시키는 것이 좋을 것으로 사료되었다. 결론적으로 본 HPLC-UV 검출법온 KR-V 시리즈 물질들의 약물동태연구를 위한 약물 분석법의 유효한 방법으로 검토되었다.

• 한국식품과학회지
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• 제50권6호
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• pp.629-635
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• 2018

본 연구에서는 플라즈마 및 UVC 처리에 의해 매실청에 존재하는 아미그달린 저감화 공정을 개발하여 아미그달린 저감화 매실청에 대한 독성을 독성동태학적 및 14일 반복 경구투여에 의해 평가하였다. 독성동태학적 연구 결과, 플라즈마 및 UVC 처리에 의한 아미그달린 저감화 매실청 투여에 의해 아미그달린의 경구 흡수량이 약 3.7, 3.4배 감소하여 저감화 효과를 확인할 수 있었다. 아미그달린 저감화 매실청의 14일 반복 경구독성시험 결과를 종합하면, 몸무게 변화, 식이 및 물 섭취량, 절대장기 및 상대 장기 무게, 혈액학적 및 혈청학적 분석, 조직 병리학적 분석에서 유의미한 독성현상이 관찰되지 않았다. 따라서 본 연구에서 개발 플라즈마 및 UVC 처리에 의한 아미그달린 저감화 매실청의 독성영향은 없는 것으로 보이며, 이러한 공정은 매실청뿐만 아니라 아미그달린 함유 다양한 제품의 저감화 공정에 활용될 수 있을 것이다.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.170-170
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• 2003

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.242.2-242.2
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• 2001

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.307.1-307.1
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• 2001

• 한국환경성돌연변이발암원학회지
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• 제21권2호
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• pp.122-127
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• 2001

4-tert-octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. Also, OP is known to have estrogenic activity by interacting with development and functions of endocrine system. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley rats. Male rats were administered OP, by either single oral (gavage) applications of 50, 100 or 200 mg/kg body weight. or a single intravenous injections of 1, 5 or 10 mg/kg body weight. Blood samples taken at several time intervals after administration were obtained from the femoral artery. Analysis of blood samples for OP was performed by gas chromatography mass spectrometry (GC/MS). The detection limit of OP was 1.9 ng/$m\ell$ at SIM (selected ion monitoring) mode of GC/MS. Calibration curve for analysis of the concentrations of OP in plasma was (OP/butylphenol peak area ratio) = 0.0294 $\times$ (plasma cone.) + 0.028 ($r^2$= 0.9991). The OP plasma concentration was 3921 ng/$m\ell$ immediately after single intravenous application, decreased rapidly within 45 min, and was detectable at low concentration up to 6 hr after application. When administered orally in rats (50, 100 and 200 mg/kg), OP was detected in the blood early after gavage administration, indicating the rapid initial uptake from gastrointestinal tract, with Tmax obtained from 0.67~0.83 hr. Using the AUC (area under the curve) of plasma concentration vs. time, low oral bioavailabilities of 1.2, 5.0 and 5.3% were calculated for the 50, 100 and 200 mg/kg groups, respectively.

• 대한수의학회지
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• 제36권3호
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• pp.743-745
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• 1996

가축 특히 대동물에 있어서 전방수의 화학조성에 관한 보고는 극히 드물다. 따라서 본 연구에서는 한우 및 유우(Holstein)를 대상으로 전방수에 대해 화학조성을 검토하였다. 유의의 protein, urea nitrogen, creatinine, cholesterol, calcium, sodium, potassium과 chloride 등이 분석 검출되었다. 이러한 조성분포는 혈장에서 보다는 수액(cerebrospinal fluid)의 조성에 더 유사한 것으로 나타났으며, 한우 및 유우에 있어서 조성에 관한 차이는 거의 인정되지 않았다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.163-163
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• 2002

4-tert-octylphenol (OP) is surfactant additive widely used in the manufacture of a variety of detergents and plastic products, a U.S. Environmental Protection Agency (EP A) classified endocrine disruptor. The purpose of this study was developed the analytical method of OP and determined toxicokinetics parameters after i. v. and oral administration in SD rats plasma concentration of OP using HPLC.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.170-170
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• 2003

DW -224a is a fluoroquinolone antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. In order to clarify toxicokinetic profile of DW-224a, a 4-week repeated dose oral toxicokinetic study (dose level: 0, 63, 250, 1000 mg/kg) was conducted in groups of Sprague-Dawley rats.(omitted)