• Toxicological Research
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• v.8 no.2
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• pp.273-284
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• 1992

It is well known that phenytoin (PHT), a commonly prescribed anticonvulsant, has teratogenicity in experimental animals and human. The major malformation induced by PHT in mouse is cleft palate. The mechanisms of the embryotoxic effects of PHT are unknown. However, PHT and synthetic glucocorticoids share several features with respect to their teratogenicity, and it was known that PHT increased maternal corticosterone level. Therefore PHT-induced cleft palate may be mediated indirectly by elevated maternal corticosterone. Recently it was reported that secalonic acid Dinduced cleft palate and elevated endogenous corticosterone level, and that such effects were antagonized by DMSO. The purpose of this work was to investigate whether the elevated maternal corticosterone is associated with the teratogenicity of PHT in the ICR mouse fetuses by treatment with PHT or PHT plus DMSO. PHT (74mg/kg, BW) was daily administered intraperitoneally on day 10~12 of gestation with and without DMSO(2ml/kg, BW), and the fetal malformation was observed on day 18. Maternal serum corticosterone and fetal PHT levels were determined by HPLC. The results are summarized as follows. 1)The percentage of cleft palate incidense in fetuses following treatment with PHT on day 10~12 of gestation was 51.7%. 2)There was a significant decrement in the cleft palate incidence in fetuses to 30.8% in the group treated with PHT plus DMSO compared with 51.7% in that with PHT alone. 3) Maternal serum corticosterone levels following treatment with PHT on day 10~12 of gestation increased by 116~343% compared with that of vehicle control. Such effect was antagonized by DMSO. 4)PHT concentration in the fetuses was not affected by DMSO. These results suggest that PHT-induced cleft-palate in fetuses seems to be closely associated with the elevation of maternal corticosterone level.

• 대한임상약리학회:학술대회논문집
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• 2005.12a
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• pp.5-5
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• 2005

• 대한임상약리학회:학술대회논문집
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• 1992.11a
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• pp.34-34
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• 1992

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.383-386
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• 1986

Enlargement of the gingiva caused by phenitoin, an anticonvulsant used in the treatment of epilepsy, occurs in some of the patients receiving the drug. Its incidence varies from 3 to 62 percent, with the greater frequencies in younger patients. The hyperplasia is usually generalized throughout the mouth, but is more severe tendency in the maxillary and mandibular anterior regions, 18 year old male patient was admitted to our Department of Dentistry with the complaint of generalized painless gingival swelling. After the consult of the N.M. and laboratory study, the gingivectomy and gingivoplasty was performed. The periodontal pack and tin foil was applied on the attached gingiva to protect a surgical site and bleeding control. We obtained a good result of improved esthetics and function.

• Journal of Pharmaceutical Investigation
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• v.18 no.1
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• pp.15-21
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• 1988

An inclusion complex of phenytoin (PT) with ${\beta}-cyclodextrin\;({\beta}-CyD)$ in molar ratio of 1 : 1 was prepared, and the interaction between host and guest molecules was confirmed by infrared spectrometry, differential scanning calorimetry and X-ray diffractometry. Suppositories were prepared by the fusion method. PT and $PT-{\beta}-CyD$ complex were added to PEG 1540 and Witepsol H-15 under the vigorous stirring at $40^{\circ}C$. Content uniformity was tested for different formulations of the PT suppositories. The release rates were dependent on the K.P. V dissolution apparatus and the dialyzing tubing method. Then, the release rates were increased in the following order: $PT-{\beta}-CyD$ complex in PEG 1540>PT in PEG 1540>$PT-{\beta}-CyD$ complex in Witepsol H-15>PT in Witepsol H-15. The area under the curve and maximum blood concentration after rectal administration were increased in the following order: $PT-{\beta}-CyD$ complex in PEG 1540>PT in PEG 1540>$PT-{\beta}-CyD$ complex in Witepsol H-15>PT in Witepsol-15.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.48-64
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• 2002

The primary recognized health risk from common deficiencies in glucose-6-phosphate dehydrogenase (G6PD), a cytoprotective enzyme for oxidative stress, is red blood cell hemolysis. Here we show that litters from untreated pregnant mutant mice with a hereditary G6PD deficiency had increased prenatal (fetal resorptions) and postnatal death. When treated with the anticonvulsant drug phenytoin, a human teratogen that is commonly used in pregnant women and causes embryonic oxidative stress, G6PD-deficient dams had higher embryonic DNA oxidation and more fetal death and birth defects. The reported G6PD gene mutation was confirmed and used to genotype fetal resorptions, which were primarily G6PD deficient. This is the first evidence that G6PD is a developmentally critical cytoprotective enzyme for both endogenous and xenobiotic-initiated embryopathic oxidative stress and DNA damage. G6PD deficiencies accordingly may have a broader biological relevance as important determinants of infertility, in utero and postnatal death, and teratogenesis.-Nicol, C. J., Zielenski, J., Tsui, L.-C., Wells, P. G. An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.195-195
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• 2001

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.241.1-241.1
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• 2001

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.127-130
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• 2004

Analytical sensitivity on TDM test is the lowest concentration that can be distinguished from background noise. The aim of study was to evaluate analytical sensitivity that is also referred to as the lower limit of detection(LLD) about difference between zero calibrator and isotonic saline sample. We tested for 10 days with zero calibrators and 0.85% saline samples while running trilevel control samples under control. Raw data divided by two groups calculated mean and standard deviation from two sample populations and analytical sensitivity by ${\bar{X}}+2SD$. In comparison with isotonic saline samples and zero calibrators, there were significant differences in phenytoin, phenobarbital and vancomycin, etc. Especially analytical sensitivity on phenytoin is at the same level as the upper limit of analytical measurement range with $40{\mu}g/mL$. We think the cause of this is matrix interference. In conclusion, we were sure that standard protocol for analytical sensitivity as lower limit of analytical measurement range on TDM test must be measured with zero standard rather than an isotonic saline sample and type 1 reagent DW for reducing matrix effects within interactions between different materials in a mixture.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.345-345
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• 1994

BBB opening 에 의란 수용성 약물 및 지용성 약물의 뇌혈관 투과 패턴을 알아보기 위해 모델약물로서 수용성 약물인 $^{99}$Tc-DTPA, 지용성 약물인 Pherlytoin을 선택하여 뇌혈관 투과성(PA)의 증가율을 검토하고자 하였다. 랫트의 좌측 외경동맥(left external carotid artery)에 혈류의 역방향으로 PE-50 catheter를 분지점에서 1-2mm 전까지 삽입하고, 1.6 molal L-(+)-arabinosg 고장액 (1580 mOsm)을 0. 12ml/sec의 일정한 속도로 30초간 infusion 한 후. $^{99}$Tc-DTPA 혹은 phenytoin 약물 용액을 대뢰정맥으로 주사하고, 대뢰동맥으로부터 약물 투여전 및 투여후 10, 30초, 1, 1.5, 2, 3. 4, 5. 7, 10분 간격으르 혈액을 채취하였으며. 마지막 채혈후 즉시 단두하여 뇌조직을 취하였다. 채취한 뇌를 좌, 우반구 및 각 부위별로 분리하고 감마 카운터와 HPLC를 이용하여 뇌증농도를 정량하였다. 또한 뇌 실질 조직내 약물량을 구하기 위해 뇌 혈관내에 존재하는 약물양을 보정하였는데, 이때 계산에 필요한 뇌증 혈액부피의 측정은 $^{99}$Tc-albumin을 이용하여 구하였다.