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Liposome Immunoassay for Determination of phenytoin

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Chinese Chemical Letters 1998年第11期9卷 0-0,0-0页

作者： Wen Yu ZHU Wen Bao CHANG Yun Xiang CI (Department of Chemistry, Peking University, Beijing 100871) Department of Chemistry Peking University Beijing 100871 China

Homogeneous liposome immunoassay for the determination of phenytoin was *** were prepared from cholesterol (CH) and phospholipids including dipalmitoyl phosphatidyl ethanolamine (DPPE) tbr conjugation with thiol-containing antibodies. Hemin chloride was entrapped in the liposome and antibody was modified by reaction with 3' (2-pyndyl-dithio) propionyl N-hydroxysuccinimide ester (SPDP) to introduce thiol groups for efficient coupling. Antibody-coupled liposomes (immunoliposomes) were incubated with phenytoin and complement, and then with hemin substrate. The amount of hemin released from immunoliposomes, which increases with concentration increase of phenytoin, can be detected rapidly by determining the fluorescence with its substrate p-hydroxyphenyl propionic acid (HPPA)and hydrogen peroxide.

关键词： Iiposome phenytoin liposome immunoassay

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Effects of duration of phenytoin administration on mRNA expression of cytochrome P450 and P-glycoprotein in the liver and small intestine of rats

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Asian Journal of Pharmaceutical Sciences 2016年第5期11卷 662-667页

作者： Atsushi Kawase Hiroyuki Tanaka Toru Otori Kenji Matsuyama Masahiro Iwaki Department of Pharmacy Faculty of PharmacyKindai University

phenytoin(5,5-diphenylhydantoin;DPH) induces expression of cytochromes P450(CYPs). Interactions between DPH and tacrolimus suggested that the persistence of CYP induction after discontinuation of DPH is dependent on the history of administration and dosing period of DPH. However, the relationship between the duration of DPH administration and expression of CYPs in the liver and small intestine of rats is not known. Alterations in levels of P-glycoprotein(P-gp;MDR1;ABCB1) as well as CYPs cause drug interactions in the small intestine. We examined the effects of the duration of DPH administration on expression of CYPs and P-gp in the liver and small intestine of rats. Rats were treated with DPH(100 mg/kg,peroral(p.o.) twice a day(b.d.)) for 2, 4, 8, and 16 d. mRNA levels of CYPs and P-gp were examined using the total RNA extracted from the liver and duodenum 2 h and 24 h after the final administration of DPH. CYP3 A activities were determined using microsomes. DPH administration for 2 d and 4 d markedly increased m RNA levels of CYPs such as CYP3 A1, CYP3 A2,CYP2 B1, and CYP2 B2 in the liver. A relatively long duration of DPH administration(8 d and16 d) resulted in abolition of the induction of hepatic CYP but increased CYP3 A activities were maintained. These results suggest that the duration of DPH administration could be an important determinant of hepatic CYP induction.

关键词： phenytoin Cytochromes P450 Microsomes mRNA Liver

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phenytoin Effects on Proliferation and Induction of IL1<i>β</i>and PGE2 in Pediatric and Adults’ Gingival Fibroblasts

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Open Journal of Stomatology 2014年第9期4卷 452-462页

作者： Surena Vahabi Masomeh Moslemi Bahareh Nazemisalman Zahra Yadegari Biotechnology Shahid Beheshti Medical University Tehran Iran Pedodontic Department Dental School Shahid Beheshti University of Medical Sciences Tehran Iran Pedodontic Department Dental School ZUMS Zanjan Iran Periodontics Department Dental School Shahid Beheshti University of Medical Sciences Tehran Iran

Background: Gingival Overgrowth (GO) is a well documented and unwanted side effect that occurs mainly as a result of certain antiseizure, phenytoin. The aim of this study was to compare the effect of phenytoin on proliferation and production of IL1β and PGE2 in cultured human gingival fibroblasts (HGF) of children and adults. Materials and Methods: Normal HGFs were obtained from 4 healthy children and 4 adult and then were cultured with phenytoin (20 mg/ml). MTT test was used to evaluate the proliferation and ELISA to determine the level of IL1β and PGE2 production by HGFs. Analysis of proliferation were assessed by Independent T-Test and ANOVA analysis was used to assess the level of IL1β and PGE2 production with an a error level less than 0.05. Results: The proliferation of HGF was not affected significantly by phenytoin in both cultured fibroblast sources (P > 0.05). phenytoin induced a significantly higher formation of IL1β and PGE2 in child’s HGFs as compared to adult’s HGFs (P phenytoin therapy. More advanced and systematic studies are needed to verify these findings.

关键词： phenytoin Gingival Overgrowth Fibroblast Interleukin Children

phenytoin-Induced Elevation of the Intracellular Calcium Concentration by Stimulation of Calcium-Sensing Receptors in Gingival Fibroblasts

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Pharmacology & Pharmacy 2013年第2期4卷 261-265页

作者： Toshimi Hattori Keisuke Nakano Toshiyuki Kawakami Department of Dental Pharmacology Matsumoto Dental University Shiojiri Japan Hard Tissue Pathology Unit Institute of Oral Science Matsumoto Dental University Shiojiri Japan.

Background:The mechanism concerning gingival overgrowth as a side effect of phenytoin, a therapeutic drug for epilepsy has been still unclear. As one of mechanisms, by measuring the intracellular calcium concentration ([Ca2+]i) of the gingival fibroblasts, it has been advocated that there is relationship between gingival overgrowth and phenytoin-induced alterations in the [Ca2+]i in gingival fibroblasts. To confirm that phenytoin elevates the [Ca2+]i, and if so, to find out its mode of action. Methods: The [Ca2+]i was measured with the Ca2+-sensitive fluorescent dye fura-2/AM. Cells were soaked in a flexiperm chamber and perfused by a saline. Drugs at appropriate concentrations were added to the perfusate. Results: phenytoin concentration-dependently elevated the [Ca2+]i. NPS2390, a calcium-sensing receptor (CaSR) blocker, significantly suppressed the phenytoin-induced [Ca2+]i elevation. U73122, a phospholipase C (PLC) inhibitor, inihibited the phenytoin-induced [Ca2+]i elevation. TMB-8, a blocker of inositol triphophate (IP3) receptors in ER, significantly depressed the phenytoin-induced [Ca2+]i elevation. m-3M3FBS, a PLC activator, enhanced the phenytoin-induced [Ca2+]i elevation. From the findings obtained, it is discussed as follows: The Ca2+-free saline and NPS2390, a CaSR antagonist, inhibited the phenytoin-induced [Ca2+]i rise;These results indicate that CaSRs exist in gingival fibroblasts and that CaSRs are involved in the phenytoin-induced [Ca2+]i rise;U73122 and TMB-8 depressed the phenytoin-induced [Ca2+]i elevation and furthermore, m-3M3FBS enhanced the phenytoin-induced [Ca2+]i elevation, showing that the Ca2+ release from the ER is involved in the phenytoin-induced [Ca2+]i elevation. Conclusion: We have concluded that phenytoin elevates the [Ca2+]i by activating CaSRs and enhancing the Ca2+ release from the Ca2+ stores in gingival fibroblasts.

关键词： phenytoin Calcium-Sensing Receptor Endoplasmic Reticulum Gingival Fibroblast Gingival Overgrowth

Effect of Cyclooxygenase Inhibition on P-Glycoprotein Expression and phenytoin Level in Brain Tissue of Pilocarpine Induced Epilepsy in Rats

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Journal of Biosciences and Medicines 2023年第8期11卷 169-191页

作者： Reham M. Elsayed Amira S. Mohamed Mona K. Tawfik Magda M. Hagras Faculty of Medicine Suez Canal University Ismailia Egypt

Background: Increased brain P-glycoprotein (P-gp) expression may play important role in resistance to antiseizure drugs. The present work aimed to overcome the drug resistance that develop due to overexpression of P-gp with subsequent increase in brain phenytoin level in epileptic rats, using either non-selective (indomethacin) or selective (celecoxib) cyclooxygenase inhibitors. Methods: Fifty-six adult male albino rats were randomly divided into seven groups. Epilepsy was induced using the lithium pilocarpine model. Rats received indomethacin (2.5 mg/kg) or celecoxib (20 mg/kg), either alone or combined with phenytoin (50 mg/kg). Seizures were evaluated using Racine score. Motor coordination was assessed using open field and rotarod tests. phenytoin brain level was measured using High Performance Liquid Chromatography (HPLC), glutamate expression was measured using Enzyme Linked Immunosorbent Assay (ELISA), ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene expression was assessed using Real Time-Polymerase Chain Reaction (RT-PCR), and immunohistochemical analysis was done for P-gp expression. Results: phenytoin combination with either indomethacin or celecoxib had improved the Racine score, motor coordination on rotarod apparatus, and open field test results. Also, phenytoin combination with either indomethacin or celecoxib decreased brain glutamate level, ABCB1 gene and P-gp expression, and increased brain phenytoin level compared to treatment with phenytoin alone. This indicated that both P-gp inhibitors indomethacin and celecoxib, increased the level of phenytoin that reached the brain of rats. However, brain uptake of phenytoin was significantly enhanced using celecoxib rather than indomethacin (CI 95%, 17.092: 32.808, P-value Conclusion: Cyclooxygenase inhibition using either celecoxib or indomethacin resulted in downregulation of P-gp expression, with subsequent increase in brain phenytoin level in epileptic rats.

关键词： P-Glycoprotein Glutamate phenytoin Indomethacin Celecoxib Epilepsy

Physico-Chemical and Microbiological Study for the Stability of phenytoin Sodium Extemporaneously Compounded Suspension in Saudi Arabia Hospitals

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Pharmacology & Pharmacy 2021年第1期12卷 1-9页

作者： Syed Ata ur Rahman Abdullah Alsaedi Abdulelah Alhusayni Abdulmalik Alqurshi Sameh Ahmed Yaser M. Alahmadi Alaa Omer M. Abdullaal Badr Ahmed A. Taher El-Sayed E. Habib Department of Pharmaceutics and Pharmaceutical Technology College of Pharmacy Taibah University Madinah Munawwarah Kingdom of Saudi Arabia Department of Pharmacy College of Health Sciences and Nursing AlRayan College Madinah Munawwarah Kingdom of Saudi Arabia Department of Pharmacognosy and Pharmaceutical Chemistry College of Pharmacy Taibah University Madinah Munawwarah Kingdom of Saudi Arabia Department of Clinical and Hospital Pharmacy College of Pharmacy Taibah University Madinah Munawwarah Kingdom of Saudi Arabia Pharmacy Department Madinah Maternity and Children Hospital Madinah Munawwarah Kingdom of Saudi Arabia Department of Microbiology and Immunology Faculty of Pharmacy Mansoura University Mansoura Egypt

Epilepsy is a chronic and the fourth most common neurological disorder which affects people of all age groups. Recently research and awareness on epilepsy-related deaths have rapidly grown over the past two decades. Many previous studies are attributed to the guidelines that apprise health care professionals in handling these deaths, but there is a relative scarcity of information accessible for clinicians and pharmacists who are responsible for manufacturing or preparing the extemporaneous anti-epileptic suspensions in the hospitals. Mostly in partial seizures, phenytoin is one of the first-choice drugs. In Saudi Arabian hospitals, the extemporaneous preparation of phenytoin suspension is common, but the hot climatic weather in Saudi Arabia possesses stability problems that should be tackled as the prepared suspension should pass all the stability tests to ensure uniform dosage of the extemporaneous formulation. In the current study, the commercial capsules were used to prepare the oral phenytoin sodium extemporaneous suspension. The physical, chemical and microbiological stability of phenytoin sodium suspension is analyzed at various temperatures.

关键词： Physical Stability phenytoin Extemporaneous Preparation Chemical Stability Epilepsy

Development of Extraction and Detection Method for a Chemotherapeutic Drug with phenytoin in Biological Samples

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Advances in Biological Chemistry 2024年第4期14卷 103-110页

作者： Michael Arnot Nicolas Brice Adan Garcia Victor Lomeli My Phuong Vu Karno Ng Department of Chemistry & Biochemistry California State University San Marcos San Marcos CA U.S.A.

Dexamethasone is classified as a corticosteroid and is commonly used among cancer patients to decrease the amount of swelling around the tumor. Among patients with cancer, in particular brain tumors, seizures can become a daily routine in their everyday lives. To counteract the seizures, an antiepileptic drug such as phenytoin is administered to act as an anticonvulsant. phenytoin and dexamethasone are frequently administrated concurrently to brain cancer patients. A previous study has shown that phenytoin serum concentration decreases when administrated concurrently with dexamethasone. Thus, it is important to monitor the concentration of these two drugs in biological samples to ensure that the proper dosages are administrated to the patients. This study aims to develop an effective extraction and detection method for dexamethasone and phenytoin. A reverse-phase high-performance liquid chromatography (HPLC) method with UV/Vis detection has been developed to separate phenytoin and dexamethasone at 219 nm and 241 nm respectively from urine samples. The mobile phase consists of a mixture of 0.01 M KH2PO4, acetonitrile, and methanol adjusted to pH 5.6 (48:32:20) and is pumped at a flow rate of 1.0 mL/min. Calibration curves were prepared for phenytoin and dexamethasone (r2 > 0.99). An efficient solid-phase extraction (SPE) method for the extraction of dexamethasone and phenytoin from urine samples was developed with the use of C-18 cartridges. The percent recovery for phenytoin and dexamethasone is 95.4% (RSD = 1.15%) and 81.1% (RSD = 3.56%) respectively.

关键词： Dexamethasone phenytoin Cancer Drug Interaction Solid Phase Extraction

Formulation of a new phenytoin-containing mucoadhesive and evaluation of its healing effects on oral biopsy ulcers

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Open Journal of Stomatology 2014年第1期4卷 5-9页

作者： Maryam Baharvand Ardeshir Lafzi Ahmad R-Mafi Jamileh-Bigom Taheri Hamed Mortazavi Somayeh Alirezaei Department of Oral Medicine Dental School Shahid Beheshti University of Medical Sciences Tehran Iran Department of Oral Medicine Islamic Azad University Dental Branch Tehran Iran Department of Periodontics Dental School Shahid Beheshti University of Medical Sciences Tehran Iran Radiation Oncologist Imam Hossein Hospital Shahid Beheshti University of Medical Sciences Tehran Iran

Background and Objective: Several studies have shown the wound healing effect of topical phenytoin, which is applied by its effect on connective tissue intracellular matrix. However, there are still some controversies about its effect on various kinds of wounds, especially in the experimental models. This study is aimed at evaluating the effect of mucoadhesive paste compared to phenytoin mucoadhesive paste on wound healing after oral biopsy. Material and Methods: In this double blind randomized clinical trial, 20 patients who were eligible for oral biopsy were allocated into the case and control groups. After the biopsy, patients having ulcers ranging between one and two centimeters were treated by simple or 1% phenytoin mucoadhesive paste. All patients were instructed to apply their paste at least three times a day for five days after the biopsy. Patients in both groups were evaluated every other day for size of the ulcer, degree of pain and diameter of the inflammatory halo. Statistical analysis was done using SPSS software and Mann-Whitney test. Results: After the second and third appointments, it was observed that the rate of wound healing and decrease in the size of the ulcers were significantly quicker in the treatment group (p = 0.001 and p = 0.003 respectively) and the patients in the phenytoin group reported less pain. Diameter of the inflammatory halo was not significantly different between two groups. Conclusion: Applying 1% phenytoin mucoadhesive paste on biopsy ulcers resulted in accelerated wound healing and decrease in pain, but had no effect on the diameter of the inflammatory halo.

关键词： Mucoadhesive Paste phenytoin Oral Ulcer

Jiedu Tongbi Tang Plus phenytoin Sodium for Severe Acute Sciatica

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Journal of Traditional Chinese Medicine 2003年第4期23卷 260-260页

作者：王德昌段树民王薇 ChinesePeople‘sPublicSecurityUniversityHospital Beijing100038 不详

Case 1: Mr. Li, a 55-year farmer from Hebeiprovince, paid his first visit on August 11, 1995. Thepatient complained of a sudden pain in the area fromhis left buttock down to the posterolateral aspect ofthe leg.

关键词： Phytotherapy Acute Disease Drug Combinations Drugs, Chinese Herbal Follow-Up Studies Humans Male Middle Aged phenytoin Sciatica

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