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https://www.readbyqxmd.com/read/29746397/impact-of-drug-interactions-on-clobazam-and-n-desmethylclobazam-concentrations-in-pediatric-patients-with-epilepsy
#1
Gabrielle R Russell, Stephanie J Phelps, Chasity M Shelton, James W Wheless
BACKGROUND: Clobazam (CLB) is approved as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in patients ≥2 years of age. It is converted to an active metabolite N-desmethylclobazam (NCLB) by CYP3A4, which is then broken down to an inactive metabolite by CYP2C19. This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy. METHODS: This was a retrospective chart review including patients >1 month of age, who received CLB between April 2012 and March 2017...
May 4, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29744790/comparative-efficacy-of-antiepileptic-drugs-for-patients-with-generalized-epileptic-seizures-systematic-review-and-network-meta-analyses
#2
Marília Silveira de Almeida Campos, Lorena Rocha Ayres, Manuela Roque Siane Morelo, Fabiana Angelo Marques Carizio, Leonardo Régis Leira Pereira
Background Valproate is a widely prescribed antiepileptic drug for generalized epilepsies, due to the extensive knowledge on its efficacy since it is on the market for many decades. However, a large number of new antiepileptic medicines was introduced into clinical practice and may be better options for treatment, considering that these medicines differ in terms of efficacy spectrum. Despite extensive research, questions regarding which medicine would constitute the first option for the monotherapy treatment of generalized epilepsy remain...
May 9, 2018: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/29742583/adjunct-ketamine-use-in-the-management-of-severe-ethanol-withdrawal
#3
Anthony F Pizon, Michael J Lynch, Neal J Benedict, Joseph H Yanta, Adam Frisch, Nathan B Menke, Greg S Swartzentruber, Andrew M King, Michael G Abesamis, Sandra L Kane-Gill
OBJECTIVES: Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. DESIGN: Retrospective observational cohort study. SETTING: Academic tertiary care hospital. PATIENTS: Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria...
May 8, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29725877/dose-dependent-teratology-in-humans-clinical-implications-for-prevention
#4
REVIEW
Gideon Koren, Matitiahu Berkovitch, Asher Ornoy
Since the inception of clinical teratology, the vast majority of scientific work has focused on identification of drugs and environmental agents causing malformations in humans as a dichotomous variable (i.e. yes or no), as well as the relative and absolute risks of such occurrences. Generally, the dose dependency of such events has not been investigated. With the establishment of large pregnancy databases, dose-dependence relationships are being uncovered for increasing numbers of medications, including valproic acid, carbamazepine, phenobarbital, lamotrigine, topiramate, and lithium...
May 4, 2018: Paediatric Drugs
https://www.readbyqxmd.com/read/29716964/nuclear-receptor-car-suppresses-gadd45b-p38-mapk-signaling-to-promote-phenobarbital-induced-proliferation-in-mouse-liver
#5
Takeshi Hori, Kosuke Saito, Rick Moore, Gordon P Flake, Masahiko Negishi
Phenobarbital (PB), a non-genotoxic hepatocarcinogen, induces hepatic proliferation and promotes development of hepatocellular carcinoma (HCC) in rodents. Nuclear receptor constitutive active/androstane receptor (NR1I3/CAR) regulates the induction and promotion activities of PB. Here, it is demonstrated that PB treatment results in dephosphorylation of a tumor suppressor p38 mitogen-activated protein kinase (MAPK) in the liver of C57BL/6 and C3H/HeNCrlBR mice. The molecular mechanism entails CAR binding and inhibition of the growth arrest and DNA-damage-inducible 45 beta (GADD45B)-MAPK kinase 6 (MKK6) scaffold to repress phosphorylation of p38 MAPK...
May 1, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29706306/psychiatric-comedication-in-patients-with-epilepsy
#6
Magdalena Bosak, Katarzyna Cyranka, Dominika Dudek, Monika Kowalik, Patrycja Mołek, Agnieszka Słowik
Psychiatric disorders are more common in patients with epilepsy than in the general population. The aims of the study were to assess the frequency and type of psychotropic drug usage in patients with epilepsy, to assess the risk factors for their use, and to assess their proconvulsive potential and the risk of interactions with antiepileptic drugs. This 20-month prospective study included patients treated at the university hospital outpatient clinic. Psychotropic drugs have been classified according to the Anatomical Therapeutic Chemical Classification System...
April 26, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29703929/non-contact-identification-and-differentiation-of-illicit-drugs-using-fluorescent-films
#7
Ke Liu, Congdi Shang, Zhaolong Wang, Yanyu Qi, Rong Miao, Kaiqiang Liu, Taihong Liu, Yu Fang
Sensitive and rapid identification of illicit drugs in a non-contact mode remains a challenge for years. Here we report three film-based fluorescent sensors showing unprecedented sensitivity, selectivity, and response speed to the existence of six widely abused illicit drugs, including methamphetamine (MAPA), ecstasy, magu, caffeine, phenobarbital (PB), and ketamine in vapor phase. Importantly, for these drugs, the sensing can be successfully performed after 5.0 × 105 , 4.0 × 105 , 2.0 × 105 , 1...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29699863/two-japanese-cases-of-epileptic-encephalopathy-associated-with-an-fgf12-mutation
#8
Ryo Takeguchi, Kazuhiro Haginoya, Yuri Uchiyama, Atsushi Fujita, Michiaki Nagura, Eri Takeshita, Takehiko Inui, Yukimune Okubo, Ryo Sato, Takuya Miyabayashi, Noriko Togashi, Takashi Saito, Eiji Nakagawa, Kenji Sugai, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto, Masayuki Sasaki
A heterozygous mutation in the fibroblast growth factor 12 (FGF12) gene, which elevates the voltage dependence of neuronal sodium channel fast inactivation, was recently identified in some patients with epileptic encephalopathy. Here we report 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). These 2 patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12 , which was identified with whole-exome sequencing...
April 23, 2018: Brain & Development
https://www.readbyqxmd.com/read/29691280/a-transcriptional-regulatory-network-containing-nuclear-receptors-and-lncrnas-controls-basal-and-drug-induced-expression-of-cytochrome-p450s-in-heparg-cells
#9
Liming Chen, Yifan Bao, Stephanie C Piekos, Kexin Zhu, Lirong Zhang, Xiao-Bo Zhong
Cytochrome P450 enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-induced levels. Some long non-coding RNAs (lncRNAs) near a transcription factor are found to participate in the regulatory functions of the transcription factors. The aim of this study is to determine whether there is a transcriptional regulatory network containing nuclear receptors and lncRNAs controlling both basal and drug-induced expression of P450s in HepaRG cells...
April 24, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29684437/sleep-dysfunction-following-neonatal-ischemic-seizures-are-differential-by-neonatal-age-of-insult-as-determined-by-qeeg-in-a-mouse-model
#10
S K Kang, S Ammanuel, S Thodupunuri, D A Adler, M V Johnston, S D Kadam
Neonatal seizures associated with hypoxic-ischemic encephalopathy (HIE) pose a challenge in their acute clinical management and are often followed by long-term neurological consequences. We used a newly characterized CD-1 mouse model of neonatal ischemic seizures associated with age-dependent (P7 vs. P10) seizure severity and phenobarbital efficacy (i.e.; PB-resistant vs. PB-efficacious respectively) following unilateral carotid ligation. The long-term consequences following untreated neonatal seizures in P7 vs...
April 20, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29680205/comparative-risk-of-major-congenital-malformations-with-eight-different-antiepileptic-drugs-a-prospective-cohort-study-of-the-eurap-registry
#11
Torbjörn Tomson, Dina Battino, Erminio Bonizzoni, John Craig, Dick Lindhout, Emilio Perucca, Anne Sabers, Sanjeev V Thomas, Frank Vajda
BACKGROUND: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. METHODS: We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP...
April 18, 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29649093/comparison-of-cyp3a4-inducing-capacity-of-enzyme-inducing-antiepileptic-drugs-using-4%C3%AE-hydroxycholesterol-as-biomarker
#12
Kristine Hole, Birgit M Wollmann, Camilla Nguyen, Tore Haslemo, Espen Molden
BACKGROUND: Enzyme-inducing antiepileptic drugs (EIAEDs) are among the clinically most important inducers of cytochrome P450 (CYP) 3A4, but there is limited evidence regarding the comparative potency of each EIAED in raising CYP3A4 activity. The aim of this study was to estimate CYP3A4-inductive potency of EIAEDs by comparing CYP3A4 activity in patients treated with carbamazepine, phenobarbital, or phenytoin. METHODS: Residual serum samples from patients treated with EIAEDs or levetiracetam were collected from a therapeutic drug monitoring service for analysis of 4β-hydroxycholesterol (4βOHC), which is an indicator of CYP3A4 activity...
April 11, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29616753/isobolographic-additivity-among-lacosamide-lamotrigine-and-phenobarbital-in-a-mouse-tonic-clonic-seizure-model
#13
Maria W Kondrat-Wróbel, Jarogniew J Łuszczki
BACKGROUND: Epilepsy is a serious neurological disease affecting about 1% of people worldwide (65 million). Seizures are controllable with antiepileptic drugs (AEDs) in about 70% of epilepsy patients, however, there remains about 30% of patients inadequately medicated with these AEDs, who need a satisfactory control of their seizure attacks. For these patients, one of the treatment options is administration of 2 or 3 AEDs in combination. OBJECTIVES: To determine the anticonvulsant effects of a combination of 3 selected AEDs (i...
March 28, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29595359/feline-hyperaesthesia-syndrome-with-self-trauma-to-the-tail-retrospective-study-of-seven-cases-and-proposal-for-integrated-multidisciplinary-diagnostic-approach
#14
Pablo Amengual Batle, Clare Rusbridge, Tim Nuttall, Sarah Heath, Katia Marioni-Henry
Case series summary This was a retrospective study on the clinical features and response to treatment in seven cats with feline hyperaesthesia syndrome (FHS) and tail mutilation. FHS is a poorly understood disorder characterised by skin rippling over the dorsal lumbar area, episodes of jumping and running, excessive vocalisation, and tail chasing and self-trauma. The majority of the cats were young, with a median age of 1 year at the onset of clinical signs, male (n = 6) and with access to the outdoors (n = 5)...
March 1, 2018: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/29588946/effective-withdrawal-of-antiepileptic-drugs-in-premonitoring-admission-to-capture-seizures-during-limited-video-eeg-monitoring
#15
Kota Kagawa, Koji Iida, Shiro Baba, Akira Hashizume, Masaya Katagiri, Kaoru Kurisu, Hiroshi Otsubo
Objective: Withdrawal of antiepileptic drugs (AEDs) is commonly applied to capture seizures in video-EEG (vEEG) monitoring for patients with infrequent but intractable seizures. Because of the half-life of AEDs, AED withdrawal during only vEEG tends to be inadequate to provoke seizures within the vEEG admission. We hypothesize that prewithdrawal of long-half-life AEDs in premonitoring admission (PMA) is safe and effective to capture seizures in the limited time of vEEG. We determined the effect of half-life on the interval between AED withdrawal and seizure occurrence...
June 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29587188/nonconvulsive-status-epilepticus-after-cessation-of-convulsive-status-epilepticus-in-pediatric-intensive-care-unit-patients
#16
Jin Chen, Lingling Xie, Yue Hu, Xinghui Lan, Li Jiang
Little is known about pediatric patients suffering from nonconvulsive status epilepticus (NCSE) after convulsive status epilepticus (CSE) cessation. The aim of this study was to identify in pediatric patients the clinical characteristics of NCSE after CSE cessation and the factors that contribute to patient outcomes. Data from clinical features, electroencephalography (EEG) characteristics, neuroimaging findings, treatments, and prognosis were systematically summarized, and the associations between clinical characteristics and prognosis were quantified...
March 24, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29565514/correlation-between-nurr1-expression-and-drug-resistance-in-the-brain-of-rats-with-epilepsy
#17
H-Y Li, F Liu, H-R Wang
OBJECTIVE: To investigate the correlation between nuclear receptor related 1 (Nurr1) expression and drug resistance in the brain of rats with epilepsy. MATERIALS AND METHODS: A total of 60 adult male Sprague-Dawley rats were selected, and the animal model of epilepsy was established by electrical stimulation. These rats were randomly divided into the control group and the drug-resistant group. The model of drug-resistant epilepsy was screened with phenytoin (PHT) and phenobarbital (PB); the hippocampus and temporal lobe cortex tissues were isolated from rats; the messenger ribonucleic acid (mRNA) and protein levels of Nurr1 in the hippocampus and cortex tissues of the two groups of rats were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry, respectively...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29559914/altered-function-and-expression-of-abc-transporters-at-the-blood-brain-barrier-and-increased-brain-distribution-of-phenobarbital-in-acute-liver-failure-mice
#18
Li Liu, Mingxing Miao, Yang Chen, Zhongjian Wang, Binbin Sun, Xiaodong Liu
This study investigated alterations in the function and expression of P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) at the blood-brain barrier (BBB) of acute liver failure (ALF) mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl- S -glutathione, respectively...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29550976/development-of-a-simultaneous-lc-ms-ms-method-to-predict-in-vivo-drug-drug-interaction-in-mice
#19
Jung Jae Jo, Jun Hyun Jo, SunJoo Kim, Jae-Mok Lee, Sangkyu Lee
Cocktail substrates are useful in investigating drug-drug interactions (DDI) that can rapidly identify the cytochrome P450 (CYP) isoforms that interact with test drugs. In this study, we developed and validated five probe drugs for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A using LC-MS/MS to determine CYP activities in mice. The five probe substrates were caffeine (2 mg/kg), bupropion (30 mg/kg), omeprazole (4 mg/kg), dextromethorphan (40 mg/kg), and midazolam (2 mg/kg) for CYP1A, CYP2B, CYP2C, CYP2D, and CYP3A, respectively...
March 17, 2018: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29548889/comparison-of-the-hepatic-and-thyroid-gland-effects-of-sodium-phenobarbital-in-wild-type-and-constitutive-androstane-receptor-car-knockout-rats-and-pregnenolone-16%C3%AE-carbonitrile-in-wild-type-and-pregnane-x-receptor-pxr-knockout-rats
#20
Corinne Haines, Lynsey R Chatham, Audrey Vardy, Clifford R Elcombe, John R Foster, Brian G Lake
A number of chemicals produce liver and thyroid gland tumours in rodents by nongenotoxic modes of action (MOAs). In this study the hepatic and thyroid gland effects of the constitutive androstane receptor (CAR) activator sodium phenobarbital (NaPB) were examined in male Sprague-Dawley wild type (WT) rats and in CAR knockout (CAR KO) rats and the effects of the pregnane X receptor (PXR) activator pregnenolone-16α-carbonitrile (PCN) were examined in WT and PXR knockout (PXR KO) rats. Rats were either fed diets containing 0 (control) or 500 ppm NaPB or were dosed with 0 (control) or 100 mg/kg/day PCN orally for 7 days...
March 13, 2018: Toxicology
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