Administration Of Phenytoin Research Articles

Diagnostic pathway and management of first seizures in infants with Sturge-Weber syndrome.

Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment. A single-centre case series of 49 infants explored early SWS care. Ninety-two per cent of children developed seizures aged 0 to 3 years; 55% of cases were before diagnostic magnetic resonance imaging (MRI) or tertiary referral. Delay in SWS diagnosis affected 31% of infants because of a lack of gadolinium enhancement for initial MRI. First seizures were frequently prolonged, with phenytoin administration necessary in 46%. Presymptomatic antiseizure medication prophylaxis (n = 8/49) decreased seizure burden. No patients on antiseizure medication prophylaxis suffered status epilepticus for longer than 30 minutes, and half of them (n = 4) had not developed seizures at last follow-up (aged 2-10 years). A parental survey enabled further service evaluation. Eighty-three per cent of parents considered local clinicians' understanding of SWS inadequate: 61% felt insufficiently informed about SWS and 81% received no epilepsy education before seizures. To overcome the identified shortfalls, guidelines towards improving and standardizing SWS management are proposed.

Association between CYP2C9 and CYP2C19 Polymorphism, Metabolism, and Neurotoxicity after Administration of Phenytoin: A Systematic Review

Abstract—Phenytoin is an antiepileptic drug (AED) metabolized by cytochrome P450 enzymes, especially by CYP2C9 (90%) and CYP2C19 (10%), where both enzymes are polymorphic so that they can undergo polymorphism and it can change the metabolic rate of the drug. Phenytoin is one of the drugs whose risk of side effects may increase due to its narrow therapeutic window of 10-20 µg/mL if the metabolism is slow. The main literature was taken from publications through the library databases in 2017 – 2021. Studies and reviews describing the metabolism, CYP2C9 and CYP2C19 polymorphisms, and neurotoxicity of phenytoin were included, and unrelated research were excluded. There were 18 of 853 articles describing CYP2C9 and CYP2C19 polymorphisms, metabolism, and neurotoxicity events associated with phenytoin used. The authors conclude that based on the results from various literature, there is an association between CYP2C9 and CYP2C19 polymorphism, metabolism, and neurotoxicity after Phenytoin administration with CYP2C9*2 and CYP2C9*3 types of polymorphisms for CYP2C9 and CYP2C19*2 and CYP2C19*3 types for CYP2C19*3 enzymes which can slow down the phenytoin metabolism and increase its concentration in serum so that the risk of causing neurotoxicity.
 Keywords: CYP2C9, CYP2C19,metabolism, neurotoxicity, phenytoin
 
 Abstrak—Fenitoin merupakan obat antibangkitan yang dimetabolisme oleh enzim sitokrom P450 terutama oleh CYP2C9 (90%) dan CYP2C19 (10%), dimana kedua enzim tersebut bersifat polimorfik sehingga dapat mengalami polimorfisme dan dapat mempengaruhi laju metabolisme obat. fenitoin merupakan salah satu obat yang risiko efek sampingnya dapat meningkat jika metabolismenya lambat karena jendela terapeutiknya yang sempit, yaitu 10-20 µg/mL. Literatur utama diambil dari publikasi melalui database perpustakaan tahun 2017 – 2021. Penelitian dan ulasan yang menggambarkan metabolisme, polimorfisme CYP2C9 dan CYP2C19, dan neurotoksisitas fenitoin, dan penelitian yang tidak terkait dikeluarkan. Terdapat 18 dari 853 artikel yang menjelaskan polimorfisme CYP2C9 dan CYP2C19, metabolisme, dan kejadian neurotoksisitas terkait dengan fenitoin yang digunakan. Peneliti menyimpulkan bahwa berdasarkan hasil dari berbagai literatur, terdapat hubungan antara polimorfisme, metabolisme, dan neurotoksisitas CYP2C9 dan CYP2C19 setelah pemberian fenitin dengan jenis polimorfisme CYP2C9*2 dan CYP2C9*3 untuk CYP2C9 dan CYP2C19*2 dan CYP2C19*3 jenis enzim CYP2C19*3 yang dapat memperlambat metabolisme fenitoin dan meningkatkan konsentrasinya dalam serum sehingga berisiko menyebabkan neurotoksisitas.
 Kata kunci: CYP2C9, CYP2C19, fenitoin, metabolisme, neurotoksisitas

Impact of an enteral nutrition holding guideline on daily nutrition goals in patients taking phenytoin.

Concomitant administration of enteral nutrition (EN) and phenytoin decreases phenytoin absorption. Concerns over impaired nutrition, however, may prevent EN from being held surrounding phenytoin administration. This study aimed to evaluate whether EN holding guidelines impacted nutrition goal achievement in patients taking phenytoin. Adult patients administered enteral phenytoin for acute or chronic seizures while receiving EN during a neurocritical care admission 6 months before and after EN holding guideline implementation were eligible. Patients without phenytoin concentrations or a clinical registered dietitian assessment were excluded. The primary outcome was the percentage of nutrition daily goals attained before and after implementation. Secondary end points included the incidence of hypoglycemia, differences in measured phenytoin concentrations, and rates of therapeutic (10-20 mcg/ml) and high-therapeutic (15-20 mcg/ml) concentration attainment. Concentrations were adjusted for hypoalbuminemia using the Winter-Tozer equation. Fifty-five patients representing 412 patient days and 1110 phenytoin administrations were included with 29 preimplementation and 26 postimplementation patients. Median percent attainment of daily EN goals was consistent preimplementation and postimplementation (86% vs 83%, P = 0.48). No significant change in rates of days with hypoglycemia was observed. Adjusted phenytoin concentrations were similar before and after implementation (14.1 vs 15.2 mcg/ml, P = 0.45), but the preimplementation cohort had a lower proportion of high-therapeutic concentrations (23% vs 36%, P = 0.018). Holding EN for phenytoin did not impact attainment of daily nutrition goals and was not associated with increased rates of hypoglycemia. This is the first study to evaluate the effect of EN holding on nutrition goals in patients receiving phenytoin.

Comparative efficacy of intravenous levetiracetam and phenytoin in status epilepticus: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND Status epilepticus (SE) is a neurological emergency, with the current guidelines for second-line anticonvulsants may include phenytoin, levetiracetam, valproic acid, and phenobarbital. However, some studies suggest that levetiracetam may be better at stopping seizures in SE. This study aimed to compare the efficacy of intravenous (IV) levetiracetam and phenytoin in SE.
 METHODS We searched PubMed, ScienceDirect, Cochrane, and Google Scholar for randomized controlled trials (RCTs) on administering IV levetiracetam or phenytoin in patients with SE. RCTs were screened using eligibility criteria, and their quality was assessed using the Cochrane risk of bias tool. Heterogeneity was assessed using the I² test, and publication bias was evaluated using Egger’s test. All analyses were performed using Review Manager version 5.4 (The Cochrane Collaboration, UK) and Stata 17 (StataCorp LLC, USA).
 RESULTS 12 RCTs involving 2,137 patients (1,099 receiving levetiracetam) met the inclusion criteria. Pooled analysis showed that levetiracetam therapy had a significantly higher rate of seizure cessation than phenytoin (RR: 1.10, 95% CI = 1.05−1.14, p = 0.02, I² = 51%). Less adverse events were observed in the levetiracetam group (9.34%) than in the phenytoin group (11.62%; RR: 0.82, 95% CI = 0.66–1.02, p = 0.07). However, there was no significant difference regarding IV levetiracetam or phenytoin administration with the incidence of admission to critical care (RR: 1.01; 95% CI = 0.93–1.10, p = 0.80) and mortality (RR: 1.08; 95% CI = 0.54–2.15; p = 0.82).
 CONCLUSIONS IV levetiracetam was significantly better in the cessation of seizures in SE patients than phenytoin.

Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain

Neuropathic pain remains a clinical challenge due to its complex and not yet fully understood pathomechanism, which result in limited analgesic effectiveness of the management offered, particularly for patients with acute, refractory neuropathic pain states. In addition to the introduction of several modern therapeutic approaches, such as neuromodulation or novel anti-neuropathic drugs, significant efforts have been made in the repurposing of well-known substances such as phenytoin. Although its main mechanism of action occurs at sodium channels in excitable and non-excitable cells and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level and how it influences morphine-induced analgesia have not been clarified, both being crucial from a clinical perspective. We demonstrated that single and repeated systemic administrations of phenytoin decreased tactile and thermal hypersensitivity in an animal model of neuropathic pain. Importantly, we observed an increase in the antinociceptive effect on thermal stimuli with repeated administrations of phenytoin. This is the first study to report that phenytoin improves morphine-induced antinociceptive effects and influences microglia/macrophage activity at the spinal cord and dorsal root ganglion levels in a neuropathic pain model. Our findings support the hypothesis that phenytoin may represent an effective strategy for neuropathic pain management in clinical practice, particularly when combination with opioids is needed.

Transcranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model

The efficacy of many anti-epileptic drugs, including phenytoin (PHT), is reduced by plasma protein binding (PPB) that sequesters therapeutically active drug molecules within the bloodstream. An increase in systemic dose elevates the risk of drug side effects, which demands an alternative technique to increase the unbound concentration of PHT in a region-specific manner. We present a low-intensity focused ultrasound (FUS) technique that locally enhances the efficacy of PHT by transiently disrupting its binding to albumin. We first identified the acoustic parameters that yielded the highest PHT unbinding from albumin among evaluated parameter sets using equilibrium dialysis. Then, rats with chronic mesial temporal lobe epilepsy (mTLE) received four sessions of PHT injection, each followed by 30 min of FUS delivered to the ictal region, across 2 weeks. Two additional groups of mTLE rats underwent the same procedure, but without receiving PHT or FUS. Assessment of electrographic seizure activities revealed that FUS accompanying administration of PHT effectively reduced the number and mean duration of ictal events compared to other conditions, without damaging brain tissue or the blood–brain barrier. Our results demonstrated that the FUS technique enhanced the anti-epileptic efficacy of PHT in a chronic mTLE rodent model by region-specific PPB disruption.

Interaction of Phenytoin with Enteral Formulas, Proteins, and Dietary Fiber in Vitro and in Vivo

Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R® were co-administered, the time to maximum plasma concentration (Tmax) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC0-6 h) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ®. These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC0-6 h. These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.

A Rare Complication of Intravenous Phenytoin Induced Purple Glove Syndrome

Purple Glove Syndrome is a relatively uncommon complication of intravenous phenytoin administration withclinical manifestations of pain, edema, and purple-blue discoloration at the injection site. Here we report a caseof Purple Glove syndrome induced by intravenous administration of phenytoin. The case report describes about a75-year-old male, who presented to the Emergency Department with chief complaints of generalized tonic - clonicseizures for which he was managed with Inj. Phenytoin. Later patient sensorium improved and 4 hours later thepatient had pain and swelling over the left hand and wrist distal to the IV cannula site followed by reddish-purplediscoloration over the edematous site. Left upper limb Doppler was done & it showed left-hand cellulitis with noevidence of thrombus. Then the patient was reassured and treated with removal of IV cannula, left-hand elevation,warmth application, analgesics and change of antiepileptics. Such medications like phenytoin should be handledcarefully to avoid difficulties in the future. Early detection, rapid monitoring, and management are essential.

Purple Glove Syndrome- A Catastrophic Complication of Phenytoin Injection

Purple Glove Syndrome (PGS) is a rare complication of intravenous phenytoin administration which is illustrated by delayed soft tissue injury of the skin conterminous to the point or distal to the site of intravenous phenytoin infusion. The clinical features of PGS include pain, oedema, and bluish discolouration over the extremity. The present case report describes about a 60-year-old male, who presented to the Emergency Department with the chief complaints of generalised tonic clonic seizures, lasting for 10 mins, for which he was managed with inj. phenytoin sodium. The computed tomography scan of brain revealed right-sided subdural haematoma. After 24 hours of hospital stay, the patient started complaining of severe pain in the arm and forearm. There was purple-bluish discolouration around the intravenous site, peripheral oedema and pain. The various risk factors linked to PGS, include old age and large and multiple doses of phenytoin.

Anti-Epileptic Drug Target Perturbation and Intracranial Aneurysm Risk: Mendelian Randomization and Colocalization Study.

In a genome-wide association study of intracranial aneurysms (IA), enrichment was found between genes associated with IA and genes encoding targets of effective anti-epileptic drugs. Our aim was to assess if this pleiotropy is driven by shared disease mechanisms that could potentially highlight a treatment strategy for IA. Using 2-sample inverse-variance weighted Mendelian randomization and genetic colocalization analyses we assessed: (1) if epilepsy liability in general affects IA risk, and (2) whether changes in gene- and protein-expression levels of anti-epileptic drug targets in blood and arterial tissue may causally affect IA risk. We found no overall effect of epilepsy liability on IA. Expression of 21 genes and 13 proteins corresponding to anti-epileptic drug targets supported a causal effect (P<0.05) on IA risk. Of those genes and proteins, genetic variants affecting CNNM2 levels showed strong evidence for colocalization with IA risk (posterior probability>70%). Higher CNNM2 levels in arterial tissue were associated with increased IA risk (odds ratio, 3.02; [95% CI, 2.32-3.94]; P=3.39×10-16). CNNM2 expression was best proxied by rs11191580. The magnitude of the effect of this variant was greater than would be expected if systemic blood pressure was the sole IA-causing mechanism in this locus. CNNM2 is a driver of the pleiotropy between IA and anti-epileptic drug targets. Administration of the anti-epileptic drugs phenytoin, valproic acid, or carbamazepine may be expected to decrease CNNM2 levels and therefore subsequently decrease IA risk. CNNM2 is therefore an important target to investigate further for its role in the pathogenesis of IA.

Treatment-refractory hypothyroidism probably secondary to concurrent phenytoin administration

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cardiovascular toxin-induced hyperglycemic and hypoarousal pathology-associated cognitive impairment: an in silico and in vivo validation

Background and purpose: Medication-induced cardiotoxicity is a significant factor in the attrition of drugs during preclinical and clinical development processes. Patients with diabetes mellitus (hyperglycemic) are more than twice as likely to experience cardiac failure. Additionally, type 2 diabetes mellitus (T2D) patients often display significant hyperarousal-related clinical anomalies such as fear, panic, nervousness, pain, and seizures. Consequently, hyperarousal in patients with inadequate metabolic outcomes (hyperglycemic conditions) is usually treated with drugs that block sodium/calcium channels, augment inhibitory (gamma-aminobutyric acid [GABA]) neurotransmission, and reduce excitatory (glutamatergic) neurotransmission. These perilous combined clinical-pathological conditions of hyperglycemia and hypoarousal may result in severe learning disabilities and cognitive impairment. Unfortunately, only a few studies have investigated the synergistic effects of hypoarousal and hyperglycemia on cognition. Methods: General behavioral assessment, plus maze, Y-maze spontaneous alternation, Hebb-Williams maze and Passive avoidance paradigm were evaluated in this study. The current study assessed the in silico structural properties attributed to its pharmacodynamic actions and interaction with Gamma-aminobutyric acid (GABA) and insulin receptors using Schrodinger and LigPrep software. Results: The administration of alloxan and phenytoin induced significant learning and cognitive deficiencies. Based on the in silico studies, alloxan is a better drug to induce hyperglycemia as compared to the well-established hyperglycemic agent, streptozotocin (STZ). Conclusions: The current study indicated that administering alloxan and phenytoin to rodents can serve as a valid animal model to understand the pathophysiology associated with hypoarousal and hyperglycemia-mediated cognitive impairment and to identify novel therapeutic interventions for hyperglycemic and hypoarousal-related learning and cognitive deficiency.

PBPK perspective on alternative CYP3A4 inducers for rifampin.

PBPK perspective on alternative CYP3A4 inducers for rifampin.

Effect of Phenytoin and Vitamin C on Granulation Tissue Thickness and Total Lymphocyte Infiltration in Enterocutaneous Fistula: In Vivo Study

Background: Enterocutaneous fistula (ECF) is still a problem in the surgical field because it causes high morbidity and mortality. The rate of closure of the ECF without surgical intervention in the evolving era of wound care and with parenteral nutrition has been reported to vary, with most studies showing closure rates in the 20 to 30% range. The administration of phenytoin and vitamin C is expected to be one of the modalities in the non-operative treatment of enterocutaneous fistulas. This study aims to assess the effect of phenytoin and vitamin C on granulation tissue thickness and the amount of lymphocyte infiltration in enterocutaneous fistulas.&#x0D; Methods: This study is an experimental study with a post-test only with a control group design. A total of 24 rats were divided into control groups, P1 (phenytoin+ vitamin c), P2 (phenytoin), and P3 (vitamin c). Histopathological assessment of granulation tissue thickness and lymphocyte infiltration was performed. Data analysis was performed using SPSS with univariate and bivariate methods.&#x0D; Results: The P1 group showed the thickest average thickness of granulation tissue compared to all groups. The P1 group showed a lower number of lymphocyte infiltration cells than all groups.&#x0D; Conclusion: The administration of phenytoin and vitamin C was effective in increasing the thickness of granulation tissue and reducing lymphocyte cells in enterocutaneous fistulas.

Efficacy of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children.

Phenytoin is one of the most used antiepileptic drugs (AEDs), but it has serious potential side effects and drug interactions. Although studies have shown levetiracetam to have a much lower side-effect profile, its efficacy when compared with phenytoin is debatable. In our study, we aimed to determine the factors that cause seizure recurrence and to compare the efficacy of levetiracetam and phenytoin in the treatment of convulsive status epilepticus (CSE) and acute repetitive seizures (ARS). In this study, 185 patients diagnosed with CSE or ARS and aged between 1month and 18years who received intravenous levetiracetam or phenytoin as a second-line AED were retrospectively evaluated. A total of 185 patients were included in the study, 85 (45.9%) girls and 100 (54.1%) boys.While 54.1% (n = 100) of the patients were given phenytoin, levetiracetam was administered to 45.9% (n = 85) of them. The rates of cessation of seizure and prevention of seizure recurrence for 24h were 84% for phenytoin and 78.8% for levetiracetam, without a significant difference (p > 0.05). Having active seizures on admission to the emergency department and an age of < 36months were significantly related to seizure recurrence (p < 0.01). Our results support that the intravenous administration of levetiracetam as the second-line treatment for CSE and ARS in children is as effective as the intravenous administration of phenytoin.

Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone.

Oligodendrocyte loss and myelin sheet destruction are crucial characteristics of demyelinating diseases. Phenytoin promotes the proliferation of endogenous neural precursor cells in the ventricular-subventricular zone in the postnatal brain that help restore the oligodendroglial population. This study aimed to evaluate whether phenytoin promotes myelin recovery of the corpus callosum of demyelinated adult mice. CD1 male mice were exposed to a demyelinating agent (0.2% cuprizone) for 8weeks. We assembled two groups: the phenytoin-treated group and the control-vehicle group. The treated group received oral phenytoin (10mg/kg) for 4weeks. We quantified the number of Olig2 + and NG2 + oligodendrocyte precursor cells (OPCs), Rip + oligodendrocytes, the expression level of myelin basic protein (MBP), and the muscle strength and motor coordination. The oligodendroglial lineage (Olig2 + cells, NG2 + cells, and RIP + cells) significantly increases by the phenytoin administration when compared to the control-vehicle group. The phenytoin-treated group also showed an increased expression of MBP in the corpus callosum and better functional scores in the horizontal bar test. These findings suggest that phenytoin stimulates the proliferation of OPCs, re-establishes the oligodendroglial population, promotes myelin recovery in the corpus callosum, and improves motor coordination and muscle strength.

The Effect of Topical and Oral Phenytoin on Increasing Wound Healing of Enterocutaneus Fistula in Wistar Rat

BACKGROUND: Enterocutaneous fistula is an abnormal connection between gastrointestinal tract with skin or wound and studies showed low numbers of spontaneous fistula closure (20–30%) despite proper wound treatment and nutrition with high morbidity and mortality rate in fistula repair operation. Phenytoin, commonly used as an anticonvulsant, has shown its effects on wound healing process such as promoting fibroblast activities, formation of granulation tissue, reduction of collagenase activities, increasing collagen production, and other connective tissue components, reducing bacterial colonization, and reducing wound exudate. AIM: To assess the effects of phenytoin in enterocutaneous fistula wound healing in Wistar rats (Ratus norvegicus). MATERIALS AND METHODS: This is an experimental study with randomized post-test only design on 20 Winstar rats. A 5 mm enterocutaneous fistula was made on the rat’s stomach and the rats were assigned randomly into three groups: K (control), P1 (10% phenytoin ointment), and P2 (0.03 mg/g oral phenytoin). The groups were terminated on day 7 and wound histological slides were made. The data were analyzed using SPSS software. RESULTS: The delta diameter is highest in P1 group (mean + SD 0.928 + 0.078), followed by P2 (mean + SD 0.770 + 0.145), and control (mean + SD 0.411 + 0.120). There is a significant difference, p &lt; 0.05 (0.000), between P1 and P2, indicating that oral phenytoin is more effective in collagen formation than topical phenytoin. There is no significant difference between P1 and P2, p &lt; 0.05 (0.269), indicating that oral phenytoin is not more effective than topical phenytoin in granulation tissue in enterocutaneous fistula in Wistar rats. CONCLUSION: Administration of topical and oral phenytoin was effective in increasing granulation tissue thickness, increasing collagen amount in wound tissue, and reducing the diameter of enterocutaneous fistulas in Wistar rats compared with control on the seventh day.

Topical phenytoin administration accelerates the healing of acetic acid-induced colitis in rats: evaluation of transforming growth factor-beta, platelet-derived growth factor, and vascular endothelial growth factor.

Ulcerative colitis (UC), limited to the colon's innermost lining, has become a global health problem. Immunomodulatory and monoclonal antibodies are used to treat UC despite their side effects and limitations. Phenytoin is used to heal wounds owing to its effects on growth factors, collagen, and extracellular matrix synthesis. This study aimed to evaluate the effect of topical phenytoin administration in UC. Phenytoin was administered in two doses during the treatment. Eighty male Wistar rats (230-280g) were divided randomly into ten groups of sham, control, hydrocortisone, phenytoin 1%, and 3% groups in 6- or 12-day treatment protocols. The UC model was induced by the administration of acetic acid 4% into the colon. Animals were killed on the 7th and 13th postoperative days. The main outcome measures included body weight loss, microscopic score, and ulcer index measured using specific criteria. Growth factors were measured by western blotting. Results illustrated that body weight loss was reversed in the treatment groups. Ulcer index had decreased on 6- and 12-day treatment protocols. Microscopic scores in 6-day enema treatment significantly decreased compared to the control groups. Transforming growth factor-beta (TGFβ) significantly increased in a time-dependent manner and platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) significantly increased in a time- and dose-dependent manner in phenytoin 1% and 3% in the 6- and 12-day protocols. Phenytoin dose- and time-dependently reversed weight loss. In addition, histopathological parameters included microscopic scores, and the ulcer index was decreased through the induction of growth factors TGFβ, PDGF, and VEGF and consequently accelerated ulcer healing.

Can topical phenytoin combined with tetracycline enhance the healing process in medication-related osteonecrosis of jaw? A comparative study.

Introduction:Treatment of Medication-related osteonecrosis of the jaw (MRONJ) is challenging. The aim of this study was to assess the effect of topical phenytoin on the healing process of MRONJ after debridement.Materials and Methods:In this study, patients with stage II of MRONJ were randomly allocated to two groups: Group 1 received debridement of the necrotic bone, with additional 5% topical phenytoin + tetracycline. Patients in group 2 underwent debridement and the involved area was primarily closed. Patients were evaluated after 1 (T1), 6 (T2), and 12 (T3) months. The presence of wound dehiscence (stage 0: No dehiscence, stage 1: Less than 10 mm dehiscence, stage 2: More than 10 mm dehiscence) and infection (presence or absence of pus and sinus tract) was evaluated. At the 12-month follow-up (T3), the number of patients who were asymptomatic for 3 months was documented in each group.Results:Twenty patients completed the study protocol (10 patients in each group). At T1 and T3, a significant difference was noted in the stage of healing between the two groups (P < 0.05). At T3, nine patients in group 1 and four patients in group 2 were symptom-free for 3 months. (P = 0.03).Conclusion:These results demonstrated that debridement combined with topical administration of phenytoin and tetracycline improved the healing process and relapse rate after treatment in stage II of MRONJ patients.

Investigation of the effects of post-operative intraperitoneal, oral, and rectal phenytoin administration on colorectal anastomosis in rats.

Anastomotic leakage is the most feared complication after colonic anastomosis. The purpose of the study is to determine the effects of phenytoin applied by different application routes, on the healing process of colorectal anastomoses. Wistar Albino rats were divided into Intraperitoneal Phenytoin Group, Oral Phenytoin Group (OAP), Rectal Phenytoin Group (RAP), and control groups. The molecular effect of phenytoin on the expression of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), fibroblast growth factor 2 (FGF2), and p53 genes was evaluated at mRNA and protein level. The effects of phenytoin on anastomotic bursting pressure analysis measured as well as pathohistological examinations. There are statistically significant increase in anastomotic bursting pressure values between control and application groups. Inflammatory cell infiltration of all groups increased in the intestinal anastomosis region compared to control. Collagen scores were found to be significantly higher in the OAP and RAP groups compared to the control group. mRNA of TGF-ß and FGF2 expression increased in all routes of phenytoin applications. Three different administration routes show considerably increase on the bursting pressure. Regarding the results of the expression of FGF2, TGF-β, p53, and VEGF genes, there is a significant increase FGF2 and TGF-β at mRNA and protein level in most administration routes.