• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5535-5538
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• 2012

Background: There have been case reports of oral squamous cell carcinoma arising from gingival overgrowth induced by phenytoin - an antiepileptic drug. However, a detailed analysis for the presence of mutations in p53 and ras genes, which are the two most frequently mutated genes in cancers, in phenytoin induced gingival overgrowth tissues has hitherto not been performed. Methods: Cellular DNA isolated from twenty gingival overgrowth tissues collected from patients undergoing phenytoin therapy were amplified using primers for p53 (exons 5-8) and H-ras (exons 1-2) genes. The PCR amplicons were then gel purified and subjected to direct sequencing analysis to screen for mutations. Results: Direct sequencing of twenty samples of phenytoin induced gingival growth did not identify mutations in any of the exons of p53 and H-ras genes that were analyzed. Conclusion: Our result indicates that mutational alteration of p53 and H-ras genes is infrequent in phenytoin induced gingival growth, which thus suggests a non malignant nature of this pathology. The findings in the present study are clinically significant as a large number of epileptic patients are treated with phenytoin.

• BMB Reports
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• 제40권3호
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• pp.448-452
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• 2007

We examined the contribution of CYP2C9 and CYP2C19 genotypes and drug interactions to the phenytoin metabolism among 97 Korean epileptic patients to determine if pharmacogenetic testing could be utilized in routine clinical practice. The CYP2C9 polymorphism is a wellknown major genetic factor responsible for phenytoin metabolism. The CYP219 polymorphism, with a high incidence of variant alleles, has a minor influence on phenytoin treated Koran patients. Using a multiple regression model for evaluation of the CYP2C9 and CYP2C19 genotypes, together with other non-genetic variables, we explained 39.6% of the variance in serum phenytoin levels. Incorporation of genotyping for CYP2C9 and CYP2C19 into a clinical practice may be of some help in the determination of phenytoin dosage. However, because concurrent drug treatment is common in patients taking phenytoin and many environmental factors are likely to play a role in drug metabolism, these factors may overwhelm the relevance of CYP polymorphisms in the clinical setting. Further investigations with an approach to dose assessment that includes comprehensive interpretation of both pharmacogenetic and pharmacokinetic data along with understanding of the mechanism of drug interactions in dosage adjustment is warranted.

• Molecular & Cellular Toxicology
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• 제2권2호
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• pp.120-125
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• 2006

Phenytoin is an anti-epileptic. It works by slowing down impulses in the brain that cause seizures. The recent microarray technology enables us to understand possible mechanisms of genes related to compounds which have toxicity in biological system. We have studied that the effect of a compound related to hepatotoxin in vitro system using a rat whole genome microarray. In this study, we have used a rat liver epithelial cell line WB-F344 and phenytoin as a hepatotoxin. WB-F344 was treated with phenytoin for 1 to 24 hours. Total RNA was isolated at times 1, 6 and 24h following treatment of phenytoin, and hybridized to the microarray containing about 22,000 rat genes. After analysis with clustering methods, we have identified a total of 1,455 differentially expressed genes during the time course. Interestingly, about 1,049 genes exhibited differential expression pattern in response to phenytoin in early time. Therefore, the identification of genes associated with phenytoin in early response may give important insights into various toxicogenomic studies in vitro system.

• 한국임상약학회지
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• 제3권2호
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• pp.139-145
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• 1993

This study was attempted to investigate the pharmacokinetics of phenytoin(4mg/kg iv,) in rabbits pretreated with diltiazem(l and 2.5mg/kg) for 7 days. The plasma concentration and area under the curve(AUC) of phenytoin were increased significantly(p<0.05) in rabbits pretreated with diltiazem(2.5mg/kg) compared with those of control rabbits. Volume of distribution and total body clearance were decreased significantly(p<0,05) in rabbits pretreated with diltiazem compared with those of control rabbits. From the results of this experiment, it is desirable that dosage ragimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin will be administered with diltiazem in clinical practice.

• 대한임상독성학회지
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• 제4권2호
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• pp.128-130
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• 2006

Phenytoin has been used globally as an effective anticonvulsant. Among its adverse effects, peripheral neuropathy including polyneuropathy has sometimes been reported. We report a case of sensorimotor polyneuropathy associated with high serum level and long-term phenytoin therapy. A 29-year-old male presented with motor weakness in all extremities. He was treated with phenytoin (400 mg/day) for about eight years because of generalized tonic clonic seizure. During none conduction assessment, sensorimotor polyneuropathy was discovered.

• Toxicological Research
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• 제7권1호
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• pp.1-12
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• 1991

The phenotyping of cytochrome P-450 in hepatic mivrosomes induced by phenytoin in the rats was carried out by using several monoclonal antibodies (MAbs) against specific P-450 isozymes. Phenytoin (180 mg/kg) was administered intrapritoneally for three consecutive days to the male Sprague-Dawley rats(100-120g). Solid phase radio-immunoassay showed higher binding affinity of MAb PB 2-66-3 and PCN 2-13-1 to the microsomes from phenytoin treated rats than those to from untreated rats, which was comparable to the level in phenobarbital induced rat hepatic microsomes.

• Archives of Pharmacal Research
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• 제14권1호
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• pp.35-40
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• 1991

(R) (+) and (S) (-) $4-^2H$-phenytoin have been used as substrates for the determination of the percentage of deuterium retention (NIH shift) after para-hydroxylation of the substrates in rat. By using GC-MS analyses, the percentages of deuterium retention were found to be 69% and 70% for the (R) and (S) phenyl rings, respectively. The results add additional evidence for the involvement of arene oxide in the oxidation of the pro (R) and pro (S) phenyls of phenytoin. The oxidation process of each ring could be mediated by independent enzyme systems, a rapid oxidative enzyme for the pro (S) phenyl and a slow oxidative enzyme for the pro (R) phenyl.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2743-2746
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• 2013

Background: Dilantin sodium (phenytoin) is an antiepileptic drug, which is routinely used to control generalized tonic clonic seizure and partial seizure episodes. A few case reports of oral squamous cell carcinomas arising from regions of phenytoin induced gingival overgrowth (GO), and overexpression of mitogenic factors and p53 have presented this condition as a pathology with potential to transform into malignancy. We recently investigated the genetic status of p53 and H-ras, which are known to be frequently mutated in Indian oral carcinomas in GO tissues and found them to only contain wild type sequences, which suggested a non-neoplastic nature of phenytoin induced GO. However, besides p53 and H-ras, other oncogenes and tumor suppressors such as PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$, are frequently altered in oral squamous cell carcinoma, and hence are required to be analyzed in phenytoin induced GO tissues to be affirmative of its non-neoplastic nature. Methods: 100ng of chromosomal DNA isolated from twenty gingival overgrowth tissues were amplified with primers for exons 9 and 20 of PIK3CA, exons $1{\alpha}$, $1{\beta}$ and 2 of p16INK4a and p14ARF, and exon 2 of $p21^{Waf1/Cip1}$, in independent reactions. PCR amplicons were subsequently gel purified and eluted products were sequenced. Results: Sequencing analysis of the twenty samples of phenytoin induced gingival growth showed no mutations in the analyzed exons of PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$. Conclusion: The present data indicate that the mutational alterations of genes, PIK3CA, p14ARF, p16INK4a and $p21^{Waf1/Cip1}$ that are frequently mutated in oral squamous cell carcinomas are rare in phenytoin induced gingival growth. Thus the findings provide further evidence that phenytoin induced gingival overgrowth as a non-neoplastic lesion, which may be considered as clinically significant given the fact that the epileptic patients are routinely administered with phenytoin for the rest of their lives to control seizure episodes.

• The Korean Journal of Pain
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• 제12권1호
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• pp.119-122
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• 1999

Glossopharyngeal neuralgia is a rare syndrome that involves episodic bursts of pain in the sensory distributuion of the ninth cranial nerve. The nature of the pain is characterized by excruciating shock-like pain in the region of the tonsillar fossa or pharynx and can radiate to the ear or the angle of the jaw. Like trigeminal neuralgia, glossopharyngeal neuralgia typically responds to anticonvulsant agents such as carbamazepine. However, dose of carbamazepine needs to be increased gradually to avoid side effects. If the patient can not tolerate until effective carbamazepine level is reached, phenytoin can be administered intravenously at the same time that oral carbamazepine therapy is begun. We present fifty-three year old female patient suffering from glossopharyngeal neuralgia who did not respond to initial carbamazepine therapy, but responded to concomitant intravenous infusion of phenytoin.

• Journal of Korean Neurosurgical Society
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• 제29권12호
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• pp.1673-1676
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• 2000

Anticonvulsant hypersensitivity syndrome is a rare but fatal complication. It manifests as fever, skin rash, lymphadenopathy, and hepatitis. Phenytoin, phenobarbital, and carbamazepine are the most frequently involved drugs. We here report a case of phenytoin-induced anticonvulsant hypersensitivity syndrome. A 37-year-old woman presented with fever and generalized skin rash, 3 weeks following commencement of phenytoin 400mg daily for treatment of seizure after superficial temporal artery-middle cerebral artery(STA-MCA) anastomosis for moyamoya disease. Her temperature was $39.3^{\circ}C$ and her face was edematous. Laboratory findings showed elevated hepatic enzymes and eosinophilia. Blood and urine culture were all negative. Initially, prednisolone was commenced at 30 mg daily. But fever and skin rash did not improved and hepatic function was more aggravated. After increasing dose of steroid(methylprednisolone 125mg/day), fever and skin rash disappeared and hepatic enzymes returned to normal range.