Search Our Scientific Publications & Authors

J Biomol Struct Dyn 2021 May 10:1-18. Epub 2021 May 10.

Laboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

The hydantoin scaffold is of substantial importance and it is commonly used in drug discovery. Herein, we report the synthesis of a novel phenytoine (a hydantoin derivative) with high yield by the reaction of phenytoin with 1-bromodecyl agent. Namely, 3-decyl-5,5- diphenylimidazolidine-2,4-dione (3DDID). Read More

Br J Clin Pharmacol 2021 Apr 9. Epub 2021 Apr 9.

Faculty of Medicine, University of Queensland, Brisbane, Australia.

Aims: Equations to calculate albumin-adjusted total concentrations have been validated to correlate with measured free concentrations for both phenytoin and valproate, but there is a lack of data to assess correlation with clinical outcomes. We aimed to assess the association of hypoalbuminaemia and albumin-adjusted total concentrations with concentration-dependent toxicity for phenytoin and valproate and review the impact on management decisions following concentration monitoring in hypoalbuminaemia.

Methods: Patients undergoing concentration monitoring for phenytoin or valproate between January and December 2018 were included. Read More

Epileptic Disord 2021 Apr 2. Epub 2021 Apr 2.

Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.

Comorbidity between epilepsy and infectious diseases in children is frequent. Pharmacokinetic drug-drug interactions (DDIs) between antiseizure medications (ASMs) and anti-infectives can occur and influence their efficacy or cause toxicity. All potential DDIs between ASMs and antimicrobial agents used in children were identified through consultation of drug compendia. Read More

Indian J Anaesth 2021 Feb 10;65(2):164-165. Epub 2021 Feb 10.

Department of Anaesthesiology, AIIMS, Patna, Phulwarisarif, Patna, Bihar, India.

Clin Toxicol (Phila) 2021 Jun 23;59(6):451-456. Epub 2021 Mar 23.

New Mexico Poison and Drug Information Center, Albuquerque, NM, USA.

Background: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. Read More

Front Med (Lausanne) 2021 1;8:650369. Epub 2021 Mar 1.

Minhang Hospital & Department of Clinical Pharmacy at School of Pharmacy, Fudan University, Shanghai, China.

Drug interactions are the most common preventable cause of adverse drug reaction, which may result in drug toxicity or undesired therapeutic effect with harmful outcomes to patients. Given the rising use of combination therapies, the main objectives of this study were to estimate the degree to which physicians can identify potential drug-drug interactions (PDDIs) correctly and to describe the common source of information used by physicians when they need to check PDDIs. A cross-sectional survey utilizing a self-administered online questionnaire was conducted among physicians in China. Read More

J Epilepsy Res 2020 Dec 31;10(2):96-99. Epub 2020 Dec 31.

College of Medicine, King Khalid University, Abha, Saudi Arabia.

Phenytoin (diphenylhydantoin) is a widely used antiepileptic drug for controlling both generalized and partial seizures. Reversible cerebellar symptoms, including cerebellar ataxia, have been recognized as an adverse event of phenytoin use for many years. On the other hand, cerebellar degeneration has been reported with chronic use in an epileptic patient treated with this drug. Read More

J Emerg Med 2021 Jan 5;60(1):54-57.e1. Epub 2020 Nov 5.

Department of Emergency Medicine, UC San Diego School of Medicine, San Diego, California; Division of Medical Toxicology, UC San Diego Health, San Diego, California.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) alters portal blood flow and may impact drug metabolism and bioavailability. However, little evidence has been published to provide guidance on medication alterations after TIPS procedures.

Case Report: We report a patient who developed phenytoin toxicity requiring a prolonged readmission after a TIPS procedure. Read More

Clin Pharmacokinet 2021 Jan 30;60(1):17-51. Epub 2020 Oct 30.

School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.

We aimed to review the pharmacokinetics (PK) of intravenous busulfan in paediatric patients, identify covariate factors influencing exposure, investigate evidence of changes in PK behaviour over time, and correlate exposure with efficacy and toxicity outcomes. A literature review was undertaken of original research published between 2007 and 2019, investigating the PK and pharmacodynamics (PD) of intravenous busulfan in patients ≤ 18 years of age. The review identified 41 publications characterising the PK, and 45 publications describing the PD, of busulfan. Read More

Epilepsy Res 2020 11 29;167:106471. Epub 2020 Sep 29.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. Electronic address:

Objective: The study aims to test the effect of influenza vaccination on phenytoin, CYP2C9, and IFNγ levels in epileptic patients receiving phenytoin monotherapy METHODS: Thirty-one epileptic patients receiving stable-dose phenytoin monotherapy were enrolled onto the study. Serum concentrations of phenytoin, CYP2C9, and IFNγ were compared before and after influenza immunization. The participants were given 0. Read More

Invest New Drugs 2021 Apr 13;39(2):499-508. Epub 2020 Sep 13.

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Read More

Postgrad Med J 2020 Aug 7. Epub 2020 Aug 7.

Neurology, Moffitt Cancer Center, Tampa, Florida, USA.

BMJ Case Rep 2020 Jul 20;13(7). Epub 2020 Jul 20.

Pulmonary Critical Care, Wayne State University, Detroit, Michigan, USA.

A 40-year-old woman with a history of chronic graft-versus-host-disease on immunosuppression with tacrolimus presented to the hospital with somnolence, confusion and muscle cramps over a few days. She was found to have hypertension, hyperglycaemia and acute kidney injury with an elevated blood tacrolimus level of greater than 120 ng/mL (reference range 5-15 ng/mL). Discontinuation of tacrolimus with concomitant administration of intravenous phenytoin led to the successful reduction of elevated tacrolimus concentrations and the resolution of her symptoms. Read More

Sci Rep 2020 07 9;10(1):11294. Epub 2020 Jul 9.

Renal Research Institute, 315 E, 62nd St, New York City, NY, 10065, USA.

Hemodialysis (HD) has limited efficacy towards treatment of drug toxicity due to strong drug-protein binding. In this work, we propose to infuse a competitor drug into the extracorporeal circuit that increases the free fraction of a toxic drug and thereby increases its dialytic removal. We used a mechanistic model to assess the removal of phenytoin and carbamazepine during HD with or without binding-competition. Read More

Indian J Pediatr 2021 Jan 12;88(1):85-86. Epub 2020 Jun 12.

Department of Pediatrics, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India.

Expert Opin Drug Metab Toxicol 2020 Aug 16;16(8):723-734. Epub 2020 Jul 16.

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital , Linkou, Taipei, Taiwan.

Introduction Phenytoin is a frequently used drug treatment for epilepsy. Genetic polymorphisms in the metabolism of phenytoin, particularly , are strongly associated with increased plasma concentrations and can result in toxicity. Human leukocyte antigen () alleles are well-known genetic predictors of certain antiepileptic drug-associated severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Read More

Cureus 2020 May 2;12(5):e7924. Epub 2020 May 2.

Internal Medicine, Bhagat Phool Singh Medical College, Khanpur, IND.

Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare condition, characterized by sudden onset of unilateral seizures leading to cerebral hemisphere atrophy and hemiplegia which might persist for lifetime. It is believed to be outcome of prolonged or unmanaged status epilepticus in pediatric age group. HHE is diagnosed during childhood but we report an undiagnosed case of 30-year-old male who was dealing with uncontrolled seizure, phenytoin toxicity and hemiparesis. Read More

Adv Exp Med Biol 2020 ;1195:189-198

University college of Pharmaceutical Sciences, Kakatiya University, Warangal, India.

In the present work, new indole derivatives, i.e., 5-[N,N-di alkyl amino alkoxy] azaindole 2,3- di-one derivatives, are synthesized and characterized. Read More

Food Chem Toxicol 2020 Aug 4;142:111393. Epub 2020 May 4.

Biomedical Research Centre, University Hospital, Hradec Kralove, Czech Republic; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address:

Phenytoin is a long-standing, anti-seizure drug widely used in clinical practice. It has also been evaluated in the context of many other illnesses in addition to its original epilepsy indication. The narrow therapeutic index of phenytoin and its ubiquitous daily use pose a high risk of poisoning. Read More

Aust Prescr 2020 Apr 1;43(2):61-63. Epub 2020 Apr 1.

Royal Brisbane and Women's Hospital, Brisbane.

J Toxicol Sci 2020 ;45(4):187-199

Translational Research Unit, R&D Division, Kyowa Kirin Co., Ltd.

In vitro human induced pluripotent stem (iPS) cells testing (iPST) to assess developmental toxicity, e.g., the induction of malformation or dysfunction, was developed by modifying a mouse embryonic stem cell test (EST), a promising animal-free approach. Read More

Neurotoxicology 2020 05 18;78:99-105. Epub 2020 Feb 18.

Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, The Inter-Faculty Brain Science School, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address:

Organophosphates (OPs) are widely used as pesticides and have been employed as warfare agents. OPs inhibit acetylcholinesterase, leading to over-stimulation of cholinergic synapses and can cause status epilepticus (SE). OPs poisoning can result in irreversible brain damage and death. Read More

Ther Drug Monit 2020 08;42(4):617-625

Division of Neurocritical Care, Massachusetts General Hospital; and.

Background: Phenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. Available equations are used to correct for the impact of hypoalbuminemia on unbound (free) phenytoin levels. The authors aimed to determine the accuracy of equations used to estimate free phenytoin in hospitalized patients and assess the impact of using additional clinical data. Read More

Neurochem Res 2020 May 8;45(5):1045-1061. Epub 2020 Feb 8.

Department of Pathology, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt.

The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p. Read More

Neurotoxicology 2020 05 5;78:21-28. Epub 2020 Feb 5.

Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil.

Nerium oleander Linn. is an Apocynaceae shrub which is among the most toxic ornamental plants. Although seizures are one of the symptoms associated with N. Read More

Indian J Crit Care Med 2019 Dec;23(Suppl 4):S290-S295

Department of Emergency Medicine, St. John's Medical College and Hospital, Bengaluru, Karnataka, India.

Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Read More

Pharmacol Rep 2020 Feb 20;72(1):87-95. Epub 2019 Dec 20.

Department of Pharmacology, Medical University of Lublin, Lublin, Poland.

Background: Anticonvulsant and acute toxic effects of 5-[(3-fluorophenyl)ethyl]-4-(n-hexyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPF-34)-a candidate for novel antiepileptic drug-were examined in the maximal electroshock-induced seizure (MES) model and rotarod test in mice. The interaction profile of TPF-34 with four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) was also studied in the mouse MES model.

Methods: Both ED and TD values for TPF-34 were determined at four treatment times (15, 30, 60 and 120 min after i. Read More

BMJ Case Rep 2020 Jan 12;13(1). Epub 2020 Jan 12.

Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA

A previously healthy 11-month-old infant presented to the emergency department in status epilepticus. There was no clear trigger of her seizure activity which resolved with benzodiazepines and fosphenytoin. On further review, her parents disclosed that she had been prescribed topical 4% lidocaine cream for a groin rash and was ultimately diagnosed with lidocaine toxicity in the emergency department. Read More

Epilepsy Behav 2020 02 6;103(Pt A):106862. Epub 2020 Jan 6.

Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India. Electronic address:

Aim: The present study aimed to explore the ameliorative role of alpha7 (α7) neuronal nicotinic acetylcholine receptor (nAChR) modulation in epilepsy and associated comorbidities in postpentylenetetrazole (PTZ)-kindled mice.

Material And Methods: The subconvulsive dose of PTZ (35 mg/kg, i.p. Read More