353 results match your criteria perpetrator drug


A Generic Framework for the PBPK Platform Qualification of PK-Sim and its Application to Predicting CYP3A4-mediated Drug-Drug Interactions.

CPT Pharmacometrics Syst Pharmacol 2021 May 4. Epub 2021 May 4.

Pharmacometrics/Modeling & Simulation, Pharmaceuticals, Research & Development, Bayer AG, Germany.

The success of applications of physiologically-based pharmacokinetic (PBPK) modeling in drug development and drug labeling has triggered regulatory agencies to demand rigorous demonstration of the predictive capability of the specific PBPK platform for a particular intended application purpose. The effort needed to comply with such qualification requirements exceeds the costs for any individual PBPK application. Since changes or updates of a PBPK platform would require re-qualification, a reliable and efficient generic qualification framework is needed. Read More

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Evaluation of the drug-drug interaction potential for trazpiroben (TAK-906), a D/D receptor antagonist for gastroparesis, towards cytochrome P450s and transporters.

Xenobiotica 2021 Apr 21:1-12. Epub 2021 Apr 21.

Global Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co, Cambridge, MA, USA.

Trazpiroben (TAK-906), a peripherally selective dopamine D2/D3 receptor antagonist, is being developed for the treatment of patients with gastroparesis. The potential of trazpiroben to act as a perpetrator or a victim for cytochrome P450 (CYP)- or transporter- mediated drug-drug interactions (DDIs) was evaluated following the latest regulatory guidelines.In vitro studies revealed that trazpiroben is metabolised mainly through a non-CYP pathway (56. Read More

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PBPK modeling to predict drug-drug interactions of ivosidenib as a perpetrator in cancer patients and qualification of the Simcyp platform for CYP3A4 induction.

CPT Pharmacometrics Syst Pharmacol 2021 Apr 6. Epub 2021 Apr 6.

Agios Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.

Ivosidenib is a potent, targeted, orally active, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that has been approved in the United States for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are greater than or equal to 75 years of age or ineligible for intensive chemotherapy, and those with relapsed or refractory AML, with a susceptible IDH1 mutation. Ivosidenib is an inducer of the CYP2B6, CYP2C8, CYP2C9, and CYP3A4 and an inhibitor of P-glycoprotein (P-gp), organic anion transporting polypeptide-1B1/1B3 (OATP1B1/1B3), and organic anion transporter-3 (OAT3) in vitro. A physiologically-based pharmacokinetic (PK) model was developed to predict drug-drug interactions (DDIs) of ivosidenib in patients with AML. Read More

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Attributable fractions for substance use in relation to crime.

Addiction 2021 Mar 19. Epub 2021 Mar 19.

Canadian Centre on Substance Use and Addiction, Ottawa, ON, Canada.

Aims: Building upon an existing methodology and conceptual framework for estimating the association between the use of substances and crime, we calculated attributable fractions that estimate the proportion of crimes explained by alcohol and six other categories of psychoactive substances.

Design: Cross-sectional surveys.

Setting: Canadian federal correctional institutions. Read More

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Food constituent- and herb-drug interactions in oncology: Influence of quantitative modelling on Drug labelling.

Br J Clin Pharmacol 2021 Mar 18. Epub 2021 Mar 18.

Certara UK Ltd, Simcyp Division, Sheffield, UK.

Aims: Herbal products, spices and/or fruits are perceived as inherently healthy; for instance, St. John's wort (SJW) is marketed as a natural antidepressant and patients often self-administer it concomitantly with oncology medications. However, food constituents/herbs can interfere with drug pharmacokinetics, with risk of altering pharmacodynamics and efficacy. Read More

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Comprehensive PBPK model to predict drug interaction potential of Zanubrutinib as a victim or perpetrator.

CPT Pharmacometrics Syst Pharmacol 2021 Mar 9. Epub 2021 Mar 9.

BeiGene USA, Inc, San Mateo, CA, USA.

A physiologically based pharmacokinetic (PBPK) model was developed to evaluate and predict (1) the effect of concomitant cytochrome P450 3A (CYP3A) inhibitors or inducers on the exposures of zanubrutinib, (2) the effect of zanubrutinib on the exposures of CYP3A4, CYP2C8, and CYP2B6 substrates, and (3) the impact of gastric pH changes on the pharmacokinetics of zanubrutinib. The model was developed based on physicochemical and in vitro parameters, as well as clinical data, including pharmacokinetic data in patients with B-cell malignancies and in healthy volunteers from two clinical drug-drug interaction (DDI) studies of zanubrutinib as a victim of CYP modulators (itraconazole, rifampicin) or a perpetrator (midazolam). This PBPK model was successfully validated to describe the observed plasma concentrations and clinical DDIs of zanubrutinib. Read More

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Low risk of the TMPRSS2 inhibitor camostat mesylate and its metabolite GBPA to act as perpetrators of drug-drug interactions.

Chem Biol Interact 2021 Apr 27;338:109428. Epub 2021 Feb 27.

Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Camostat mesylate, a potent inhibitor of the human transmembrane protease, serine 2 (TMPRSS2), is currently under investigation for its effectiveness in COVID-19 patients. For its safe application, the risks of camostat mesylate to induce pharmacokinetic drug-drug interactions with co-administered drugs should be known. We therefore tested in vitro the potential inhibition of important efflux (P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP, ABCG2)), and uptake transporters (organic anion transporting polypeptides OATP1B1, OATP1B3, OATP2B1) by camostat mesylate and its active metabolite 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA). Read More

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Costing alcohol-related assault in the night-time economy from a societal perspective: The case of Central Sydney.

Drug Alcohol Rev 2021 Feb 25. Epub 2021 Feb 25.

School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.

Introduction: There is a concern in many countries about violence from late-night alcohol sales and appropriate regulatory responses. However, economic losses arising from this activity rarely feature in public debate. Credible estimates are lacking because economic evaluations have not taken a 'societal perspective', costing health, policing and criminal justice outcomes. Read More

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February 2021

Clinical Investigation of Metabolic and Renal Clearance Pathways Contributing to the Elimination of Fevipiprant Using Probenecid as Perpetrator.

Drug Metab Dispos 2021 May 25;49(5):389-394. Epub 2021 Feb 25.

Novartis Institutes for Biomedical Research, Basel, Switzerland (H.M.W., T.L., G.R., and B.P.); Novartis Institutes for Biomedical Research, Cambridge, Massachusetts (M.C.); Novartis Institutes for Biomedical Research, East Hanover, New Jersey (S.K. and B.S.); and Novartis Healthcare Pvt. Ltd., Hyderabad, India (J.V.).

Fevipiprant, an oral, nonsteroidal, highly selective, reversible, and competitive prostaglandin D receptor 2 antagonist, is eliminated by glucuronidation and by direct renal excretion predominantly via organic anion transporter (OAT) 3. This study aimed to assess the effect of simultaneous UDP-glucuronosyltransferase (UGT) and OAT3 inhibition by probenecid on the pharmacokinetics of fevipiprant and its acyl glucuronide (AG) metabolite to support the dosing recommendation of fevipiprant in the presence of drugs inhibiting these pathways; however, phase III clinical trial results did not support its submission. This was a single-center, open-label, single-sequence, two-period crossover study in healthy subjects. Read More

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Absorption, Metabolism, Distribution, and Excretion of Letermovir.

Curr Drug Metab 2021 Feb 22. Epub 2021 Feb 22.

AiCuris Anti-infective Cures GmbH, Wuppertal. Germany.

Background: Letermovir is approved for prophylaxis of cytomegalovirus infection and disease in cytomegalovirus-seropositive hematopoietic stem-cell transplant (HSCT) recipients.

Objective: HSCT recipients are required to take many drugs concomitantly. The pharmacokinetics, absorption, distribution, metabolism, and excretion of letermovir and its potential to inhibit metabolizing enzymes and transporters In vitro were investigated to inform on the potential for drug‒drug interactions (DDIs). Read More

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February 2021

U.S. FDA Approved Drugs from 2015-June 2020: A Perspective.

J Med Chem 2021 Mar 22;64(5):2339-2381. Epub 2021 Feb 22.

Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151001, India.

In the present work, we report compilation and analysis of 245 drugs, including small and macromolecules approved by the U.S. FDA from 2015 until June 2020. Read More

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A meta-analytic review of the relationship between cyber aggression and substance use.

Drug Alcohol Depend 2021 04 9;221:108510. Epub 2021 Feb 9.

Department of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, United States.

Background: Prior research has demonstrated that various substances of abuse play a contributing role to acts of physical and verbal aggression. It is less clear if and to what extent substance use is associated with an increased risk in perpetrating cyber aggression, an emerging form of aggressive behavior that occurs through digital communication.

Methods: A comprehensive review of the literature resulted in 15 studies and 18 unique samples from which effect size estimates were calculated. Read More

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Psychotic symptoms in mass shootings . mass murders not involving firearms: findings from the Columbia mass murder database.

Psychol Med 2021 Feb 17:1-9. Epub 2021 Feb 17.

Department of Psychiatry, Columbia University Irving Medical Center, New York State Psychiatric Institute, 1051 Riverside Drive Unit 31, New York, NY10032.

Background: Mass shootings account for a small fraction of annual worldwide murders, yet disproportionately affect society and influence policy. Evidence suggesting a link between mass shootings and severe mental illness (i.e. Read More

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February 2021

The use of multiple keratinous matrices (head hair, axillary hair, and toenail clippings) can help narrowing a period of drug exposure: experience with a criminal case involving 25I-NBOMe and 4-MMC.

Int J Legal Med 2021 Feb 1. Epub 2021 Feb 1.

Institut de médecine légale, 11 rue Humann, 67000, Strasbourg, France.

The objective of this publication is to present the interest of collecting several keratinous specimens in order to document possible drug impairment at the time of the assault, when knowledge solely occurred 7 months after. A subject committed a murder and within minutes after the crime self-inflicted serious wounds. He was charged to the hospital where he slowly recovered. Read More

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February 2021

In vivo drug interactions of itopride and trimethylamine mediated by flavin-containing monooxygenase 3 in humanized-liver mice.

Drug Metab Pharmacokinet 2021 Apr 13;37:100369. Epub 2020 Nov 13.

Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan. Electronic address:

Flavin-containing monooxygenase (FMO) catalyzes the oxygenation of a wide variety of medicines and dietary-derived compounds. However, little information is available regarding drug interactions mediated by FMO3 in vivo. Consequently, we investigated interactions between FMO substrates in humanized-liver mice. Read More

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Physiologically-Based Pharmacokinetic (PBPK) Modelling of Transporter Mediated Drug Absorption, Clearance and Drug-Drug Interactions.

Curr Drug Metab 2021 Jan 1. Epub 2021 Jan 1.

Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge,. United Kingdom.

Membrane transporters play an important role in intestinal absorption, distribution and clearance of drugs. Additionally transporters along with enzymes regulate tissue exposures (e.g. Read More

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January 2021

Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research.

Neuropharmacology 2021 03 12;185:108442. Epub 2021 Jan 12.

Division of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia and IRCCS Mondino Foundation (member of the ERN EpiCARE), Pavia, Italy. Electronic address:

The therapeutic potential of cannabidiol (CBD) in seizure disorders has been known for many years, but it is only in the last decade that major progress has been made in characterizing its preclinical and clinical properties as an antiseizure medication. The mechanisms responsible for protection against seizures are not fully understood, but they are likely to be multifactorial and to include, among others, antagonism of G protein-coupled receptor, desensitization of transient receptor potential vanilloid type 1 channels, potentiation of adenosine-mediated signaling, and enhancement of GABAergic transmission. CBD has a low and highly variable oral bioavailability, and can be a victim and perpetrator of many drug-drug interactions. Read More

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Physiologically Based Precision Dosing Approach for Drug-Drug-Gene Interactions: A Simvastatin Network Analysis.

Clin Pharmacol Ther 2021 Jan 6;109(1):201-211. Epub 2020 Dec 6.

Clinical Pharmacy, Saarland University, Saarbrücken, Germany.

Drug-drug interactions (DDIs) and drug-gene interactions (DGIs) are well known mediators for adverse drug reactions (ADRs), which are among the leading causes of death in many countries. Because physiologically based pharmacokinetic (PBPK) modeling has demonstrated to be a valuable tool to improve pharmacotherapy affected by DDIs or DGIs, it might also be useful for precision dosing in extensive interaction network scenarios. The presented work proposes a novel approach to extend the prediction capabilities of PBPK modeling to complex drug-drug-gene interaction (DDGI) scenarios. Read More

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January 2021

[THE EDITH WOLFSON CENTER FOR VICTIMS OF SEXUAL ASSAULT - LESSONS FROM 17 YEARS OF EXPERIENCE].

Harefuah 2020 11;159(11):793-796

Department of Obstetrics and Gynecology, the Edith Wolfson Medical Center, Holon, and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Introduction: The Center for Victims of Sexual Assault at Wolfson's Medical Center is the first of its kind in Israel. It was launched in 2000 by the Department of Obstetrics and Gynecology, and has since served over 4000 victims. The center provides care by a multidisciplinary team of gynecologists, social workers, forensic physicians, and police investigators, in a single place and with a supporting atmosphere. Read More

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November 2020

Incidence and predictors of violence from clients, intimate partners and police in a prospective US-based cohort of women in sex work.

Occup Environ Med 2020 Nov 3. Epub 2020 Nov 3.

Department of Health, Behavior and Society, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Objective: Gender-based violence threatens women's health and safety. Female sex workers (FSWs) experience violence disproportionately, yet prospective data on violence predictors is lacking. In the first US-based prospective FSW cohort study, we examine incidence rates (IRs) and predictors of violence from distinct perpetrators: paying clients, non-paying intimate partners and police. Read More

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November 2020

Lethal smothering with a pillow - How 181 music festival visitors tried to kill a dummy.

Forensic Sci Int 2020 Nov 15;316:110521. Epub 2020 Oct 15.

Department of BioMechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering (3mE), Delft University of Technology, Mekelweg 2, 2628 CD, Delft, The Netherlands; Co van Ledden-Hulsebosch Center for Forensic Science and Medicine, Amsterdam, The Netherlands. Electronic address:

Purpose: Smothering to death is most often done with a soft cover, such as a pillow. This is one of the hardest to diagnose causes of death. Knowing more about how people perform such an act and whether there is any correlation between perpetrator characteristics and smothering approaches may help in solving criminal cases involving smothering. Read More

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November 2020

Combining Group-based Interventions for Intimate Partner Violence Perpetrators With Comorbid Substance Use: An Australian Study of Cross-sector Practitioner Views.

J Interpers Violence 2020 Oct 29:886260520969244. Epub 2020 Oct 29.

Monash University, Clayton, VIC, Australia.

The connection between intimate partner violence (IPV) perpetration and problematic alcohol and/ or other drug (AOD) use has been well established in public health, social work and criminology research. Despite the overwhelming evidence of the correlation between these two problem behaviors, service systems addressing these issues have historically done so in siloed approaches to practice. AOD interventions have frequently been criticized for a lack of IPV focused assessment and practice. Read More

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October 2020

Assessment of Clinical Drug-Drug Interactions of Elagolix, a Gonadotropin-Releasing Hormone Receptor Antagonist.

J Clin Pharmacol 2020 12 7;60(12):1606-1616. Epub 2020 Jul 7.

Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA.

Elagolix is an oral gonadotropin-releasing hormone receptor antagonist indicated for the management of endometriosis-associated pain and in combination with estradiol/norethindrone acetate indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women. Elagolix coadministered with estradiol/norethindrone acetate is in late-stage development for the management of heavy menstrual bleeding associated with uterine fibroids. Based on the in vitro profile of elagolix metabolism and disposition, 9 drug-drug interaction (DDI) studies evaluating the victim and perpetrator characteristics of elagolix were conducted in 144 healthy volunteers. Read More

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December 2020

Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China.

Curr Drug Metab 2021 ;22(1):5-23

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Background: Many antibiotics have a high potential for interactions with drugs, as a perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients.

Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature search was conducted to obtain human pharmacokinetics/ dispositions of the antibiotics, their interactions with drug-metabolizing enzymes or transporters, and their associated clinical drug interactions. Read More

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January 2021

In vitro evaluation of the metabolic enzymes and drug interaction potential of triapine.

Cancer Chemother Pharmacol 2020 11 28;86(5):633-640. Epub 2020 Sep 28.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15261, USA.

Purpose: To investigate the metabolic pathways of triapine in primary cultures of human hepatocytes and human hepatic subcellular fractions; to investigate interactions of triapine with tenofovir and emtricitabine; and to evaluate triapine as a perpetrator of drug interactions. The results will better inform future clinical studies of triapine, a radiation sensitizer currently being studied in a phase III study.

Methods: Triapine was incubated with human hepatocytes and subcellular fractions in the presence of a number of inhibitors of drug metabolizing enzymes. Read More

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November 2020

Physiologically based pharmacokinetic modeling to assess metabolic drug-drug interaction risks and inform the drug label for fedratinib.

Cancer Chemother Pharmacol 2020 10 4;86(4):461-473. Epub 2020 Sep 4.

Nonclinical Research and Development, Bristol Myers Squibb, Summit, NJ, USA.

Purpose: Fedratinib (INREBIC), a Janus kinase 2 inhibitor, is approved in the United States to treat patients with myelofibrosis. Fedratinib is not only a substrate of cytochrome P450 (CYP) enzymes, but also exhibits complex auto-inhibition, time-dependent inhibition, or mixed inhibition/induction of CYP enzymes including CYP3A. Therefore, a mechanistic modeling approach was used to characterize pharmacokinetic (PK) properties and assess drug-drug interaction (DDI) potentials for fedratinib under clinical scenarios. Read More

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October 2020

Drug interactions: a review of the unseen danger of experimental COVID-19 therapies.

J Antimicrob Chemother 2020 12;75(12):3417-3424

Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials. Read More

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December 2020

Drug-Drug Interaction Risk Assessment of Esaxerenone as a Perpetrator by In Vitro Studies and Static and Physiologically Based Pharmacokinetic Models.

Drug Metab Dispos 2020 09 2;48(9):769-777. Epub 2020 Jul 2.

Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan (M.Y., T.I., S.I., D.S.) and Tissue and Cell Research Center Munich, Daiichi Sankyo Europe GmbH, Martinsried, Germany (V.R., T.F.).

Esaxerenone (CS-3150) is a novel, oral, nonsteroidal, selective mineralocorticoid receptor blocker approved for the treatment of hypertension in Japan. Here, the drug-drug interaction (DDI) potential of esaxerenone was evaluated in vitro, and its impact in clinical practice was estimated. Esaxerenone exhibited time-dependent inhibition and induction of CYP3A. Read More

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September 2020

Impact of pantoprazole on absorption and disposition of hydroxychloroquine, a drug used in Corona Virus Disease-19 (Covid-19): A structured summary of a study protocol for a randomised controlled trial.

Trials 2020 Jun 29;21(1):584. Epub 2020 Jun 29.

Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany.

Objectives: Primary objective: Evaluation of the effect of the proton pump inhibitor (PPI) pantoprazole on the absorption of hydroxychloroquine (HCQ). Secondary objectives: • Evaluation of the relationship between HCQ concentrations in whole blood, plasma and intracellular concentrations in target cells - peripheral blood mononuclear cells (PBMCs). • Evaluation of HCQ as a potential perpetrator in drug-drug interactions at the level of cytochrome P450 (CYP) 3A4 and CYP2D6 (major drug metabolizing enzymes). Read More

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Physiologically-Based Pharmacokinetic (PBPK) Modeling of Buprenorphine in Adults, Children and Preterm Neonates.

Pharmaceutics 2020 Jun 23;12(6). Epub 2020 Jun 23.

Department of Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany.

Buprenorphine plays a crucial role in the therapeutic management of pain in adults, adolescents and pediatric subpopulations. However, only few pharmacokinetic studies of buprenorphine in children, particularly neonates, are available as conducting clinical trials in this population is especially challenging. Physiologically-based pharmacokinetic (PBPK) modeling allows the prediction of drug exposure in pediatrics based on age-related physiological differences. Read More

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