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Pharmacogenomics J 2022 May 19. Epub 2022 May 19.

UMR1231 GAD, Inserm, Université Bourgogne-Franche Comté, Dijon, France.

Beyond the identification of causal genetic variants in the diagnosis of Mendelian disorders, exome sequencing can detect numerous variants with potential relevance for clinical care. Clinical interventions can thus be conducted to improve future health outcomes for patients and their at-risk relatives, such as predicting late-onset genetic disorders accessible to prevention, treatment or identifying differential drug efficacy and safety. To evaluate the interest of such pharmacogenetic information, we designed an "in house" pipeline to determine the status of 122 PharmGKB (Pharmacogenomics Knowledgebase) variant-drug combinations in 31 genes. Read More

Dis Markers 2022 21;2022:7286645. Epub 2022 Apr 21.

Department of VIP Center, School and Hospital of Stomatology, Shandong University & Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012 Shandong, China.

Background: The purpose of this study was the evaluation of the potential and mechanism of phenytoin to promote differentiation of human dental pulp stem cells (hDPSC) into odontoblasts/osteoblasts.

Methods: Fourth-generation human hDPSC originating from healthy pulp of third molars was cultured in control as well as phenytoin-containing media (PHT) for 14 days. qPCR was applied to detect the expression of DSPP, DMP1, and ALP genes. Read More

Exp Brain Res 2022 May 1;240(5):1617-1627. Epub 2022 Apr 1.

Laboratorio de Neurociencias, Facultad de Psicologia, Universidad de Colima, Av. Universidad 333, 28040, Colima, COL, Mexico.

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. Read More

Ther Drug Monit 2022 04;44(2):345-350

Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany; and.

Background: Therapeutic drug monitoring (TDM) of antiseizure medications (ASMs) is widely used to guide therapy, avoid toxicity, and assess patient compliance. Commercial immunologic quantification methods are common practice; however, as they are only applicable to one specific drug and prone to cross-reacting metabolites, their practical applicability is limited. In this article, the authors proposed a high-performance liquid chromatography method using ultraviolet detection (HPLC-UV) for simultaneous quantification of 11 ASMs and active metabolites (carbamazepine, felbamate, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, zonisamide, carbamazepine-10,11-epoxide, and licarbazepine) in serum. Read More

Epilepsia 2022 Apr 18;63(4):1003-1015. Epub 2022 Feb 18.

Department of Pharmaceutical Sciences and Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Objective: As a key member of the transient receptor potential (TRP) superfamily, TRP canonical 3 (TRPC3) regulates calcium homeostasis and contributes to neuronal excitability. Ablation of TRPC3 lessens pilocarpine-induced seizures in mice, suggesting that TRPC3 inhibition might represent a novel antiseizure strategy. Among current TRPC3 inhibitors, pyrazole 3 (Pyr3) is most selective and potent. Read More

Biomed Pharmacother 2022 Feb 2;146:112377. Epub 2022 Jan 2.

Center for Engineering in Medicine and Surgery at Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States; Shriners Hospitals for Children, Boston, MA 02114, United States. Electronic address:

Drug-drug-interactions (DDIs) occur when a drug alters the metabolic rate, efficacy, and toxicity of concurrently used drugs. While almost 1 in 4 adults now use at least 3 concurrent prescription drugs in the United States, the Non-alcoholic fatty liver disease (NAFLD) prevalence has also risen over 25%. The effect of NALFD on DDIs is largely unknown. Read More

Comp Biochem Physiol C Toxicol Pharmacol 2022 Mar 3;253:109265. Epub 2022 Jan 3.

Laboratorio de Toxicología Ambiental, Facultad de Química, Universidad Autónoma del Estado de México. Paseo Colón intersección Paseo Tollocan, Colonia Residencial Colón, CP 50120 Toluca, Estado de México, Mexico.

Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Read More

Prim Care Companion CNS Disord 2021 Dec 23;23(6). Epub 2021 Dec 23.

Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

Int J Mol Sci 2021 Nov 24;22(23). Epub 2021 Nov 24.

Comparative Perinatal Development, Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

The zebrafish () embryo is gaining interest as a bridging tool between in-vitro and in-vivo developmental toxicity studies. However, cytochrome P450 (CYP)-mediated drug metabolism in this model is still under debate. Therefore, we investigated the potential of zebrafish embryos and larvae to bioactivate two known anti-epileptics, carbamazepine (CBZ) and phenytoin (PHE), to carbamazepine-10,11-epoxide (E-CBZ) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), respectively. Read More

Clin Ther 2021 12 15;43(12):2127-2135. Epub 2021 Nov 15.

Multidisciplinary Research Unit, Government Medical College Srinagar, Srinagar, Jammu and Kashmir, India. Electronic address:

Purpose: This study was conducted to examine and verify the use of saliva as an alternative matrix for monitoring phenytoin drug levels in patients with epilepsy. Drug concentrations are measured to evaluate whether a suitable drug level has been achieved to minimize the risk for toxicity, inadequate efficacy, or therapy resistance and compliance issues.

Methods: Quantitative analysis was performed by using reverse-phase HPLC after sample pretreatment with acetonitrile. Read More

Pharmacol Res 2022 01 14;175:105976. Epub 2021 Nov 14.

Unit of Pharmacology, Department of Clinical and Experimental, University of Pisa, Pisa, Italy. Electronic address:

Seizures are relatively common in cancer patients, and co-administration of chemotherapeutic and antiepileptic drugs (AEDs) is highly probable and necessary in many cases. Nonetheless, clinically relevant interactions between chemotherapeutic drugs and AEDs are rarely summarized and pharmacologically described. These interactions can cause insufficient tumor and seizure control or lead to unforeseen toxicity. Read More

Reprod Toxicol 2021 12 12;106:109-114. Epub 2021 Oct 12.

School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, NSW, 2006, Australia.

Phenytoin is a known human teratogen with unknown etiology. Several mechanisms have been proposed including disturbances in folate metabolism, induction of embryonic hypoxia following phenytoin-induced bradycardia, free radical formation following re-oxygenation and phenytoin-induced maternal hyperglycemia. Using high frequency ultrasound, we demonstrated that phenytoin induced a dramatic decrease in the heart rate of embryos. Read More

BMC Pharmacol Toxicol 2021 10 11;22(1):57. Epub 2021 Oct 11.

Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Federal University of Agriculture, P.M.B.2373, Makurdi, Benue State, Nigeria.

Background: Pharmacokinetics (PK) is the process of absorption, distribution, metabolism and elimination (ADME) of drugs. Some drugs undergo zero-order kinetics (ethyl alcohol), first order kinetics (piroxicam) and mixed order kinetics (ascorbic acid). Drugs that undergo Michaelis-Menten metabolism are characterized by either increased or decreased metabolism constant (Km) and maximum velocity (Vmax) of enzyme reaction. Read More

Epilepsia 2021 12 8;62(12):3076-3090. Epub 2021 Oct 8.

Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, Washington, USA.

Objectives: Benzodiazepines are the standard of care for the management of sustained seizure emergencies, including status epilepticus (SE) and seizure clusters. Seizure clusters are a variably defined seizure emergency wherein a patient has multiple seizures above a baseline rate, with intervening periods of recovery, distinguishing clusters from SE. Although these seizure emergencies are phenotypically distinct, the precise pathophysiological and mechanistic differences between SE and seizure clusters are understudied. Read More

Curr Neurovasc Res 2021 ;18(4):374-380

Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, China.

Background: The mossy fiber sprouting (MFS) in the dentate gyrus is a common pathological change of epilepsy. Previous studies suggested that it is associated with drug-resistant epilepsy, and mossy cells control spontaneous seizures and spatial memory.

Methods: We investigated the correlations among cognitive impairment, MFS, seizure frequency and drug resistance in a rat model of epilepsy induced by lithium-pilocarpine. Read More

Neurol India 2021 Jul-Aug;69(4):1014-1017

Department of Pharmacology, Government Medical College, Punjab, India.

Phenytoin is a commonly used antiepileptic drug for various types of seizure disorders except for absent seizures. Long-term dose-dependent neurological side effects of phenytoin therapy include cerebellar atrophy, cerebral atrophy, and brain stem atrophy. Skull hyperostosis, gum hypertrophy, and megaloblastic anemia are other known effects of long-term therapy. Read More

Neuropsychopharmacol Rep 2021 09 23;41(3):336-351. Epub 2021 Jul 23.

The Faculty of Medicine, Jazan University, Jazan, Saudi Arabia.

Background: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non-neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents. Read More

Leg Med (Tokyo) 2021 Nov 21;53:101935. Epub 2021 Jun 21.

Department of Forensic Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address:

The patient was a two-day-old female infant. The patient's mother was a primigravid in her 20 s who developed premature abruption of the normal placenta on the first day of the 33rd week of gestation. The infant was born by emergency cesarean section with severe neonatal asphyxia with a birth weight of 1928 g. Read More

Seizure 2021 Oct 6;91:117-131. Epub 2021 Jun 6.

Senior Resident, Department of Neurology, Smt. B. K. Shah Medical institute and research Centre, Sumandeep Vidyapeeth, Piparia, Waghodia, Vadodara Gujarat, 391760, India. Electronic address:

Serotonin syndrome (SS) is a drug‑induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs (AEDs) are known to have serotonergic properties and it can be hypothesized that such AEDs can cause SS. This study aims to review the literature on SS in patients receiving AEDs. Read More

Curr Drug Saf 2022 ;17(1):40-46

Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry-605006, India.

Background And Objective: Identification of the offending drug is crucial and challenging in cases of severe cutaneous adverse drug reactions (CADR) like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Poor reproducibility and varying levels of agreement have been observed among different causality assessment tools (CATs) in assessing severe CADRs. This study was conducted to examine the agreement among four different CATs in assessing cases of drug-induced SJS, TEN and SJS/TEN overlap. Read More

FASEB J 2021 07;35(7):e21693

Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Drug-induced gingival overgrowth (DIGO) is a side effect of cyclosporine A (CsA), nifedipine (NIF), and phenytoin (PHT). Nuclear receptor 4A1 (NR4A1) plays a role in fibrosis in multiple organs. However, the relationship between NR4A1 and DIGO remains unclear. Read More

J Pharm Pharm Sci 2021 ;24:277-291

Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, USA.

Purpose: Remdesivir, a drug originally developed against Ebola virus, is currently recommended for patients hospitalized with coronavirus disease of 2019 (COVID-19). In spite of United States Food and Drug Administration's recent assent of remdesivir as the only approved agent for COVID-19, there is limited information available about the physicochemical, metabolism, transport, pharmacokinetic (PK), and drug-drug interaction (DDI) properties of this drug. The objective of this in silico simulation work was to simulate the biopharmaceutical and DDI behavior of remdesivir and characterize remdesivir PK properties in special populations which are highly affected by COVID-19. Read More

J Toxicol Sci 2021 ;46(6):289-301

Faculty of Naval Medicine, Second Military Medical University (Naval Medical University), China.

Background: Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered.

Purpose: To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity. Read More

Toxicol Sci 2021 08;182(2):183-194

Drug Safety Research and Development, Pfizer Inc, San Diego, California 92121, USA.

Lorlatinib is a potent small-molecule anaplastic lymphoma kinase inhibitor approved for the treatment of patients with nonsmall cell lung cancer. In a drug-drug interaction study in healthy human participants, liver enzyme elevations were observed when a single 100 mg dose of lorlatinib was administered after multiple doses of rifampin, a strong cytochrome P450 (CYP) 3A inducer and a pregnane X receptor (PXR) agonist. A series of in vitro and in vivo studies were conducted to evaluate potential mechanisms for the observed clinical toxicity. Read More

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 11 4;87(11):4341-4353. Epub 2021 May 4.

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;23(2):229-256

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 06 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