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    11022 results match your criteria British journal of clinical pharmacology[Journal]

    1 OF 221

    Physiologically Based Pharmacokinetic Modeling of a CYP2C19 Substrate, BMS-823778, Utilizing Pharmacogenetic Data.
    Br J Clin Pharmacol 2018 Feb 22. Epub 2018 Feb 22.
    Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, NJ, 08543.
    Aims: Previous studies demonstrated direct correlation between CYP2C19 genotype and BMS-823778 clearance in healthy volunteers. The objective of the present study was to develop a PBPK model for BMS-823778 and utilize the model to predict PK and DDI in virtual populations with multiple polymorphic genes.

    Methods: The PBPK model was built and verified utilizing existing clinical data. Read More

    Incorporation of GSTA1 genetic variations into a population pharmacokinetic model for IV busulfan in paediatric hematopoietic stem cell transplantation.
    Br J Clin Pharmacol 2018 Feb 22. Epub 2018 Feb 22.
    Department of Pediatrics, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
    Aims: To develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants of GSTA1, gene coding for the main enzyme in busulfan imetabolism.

    Methods: Busulfan concentration-time data was collected from 112 children and adolescents (median 5.4 years old, range: 0. Read More

    Clinical safety, tolerability, pharmacokinetics and effects on urinary electrolyte excretion of AZD997, a novel, selective mineralocorticoid receptor modulator.
    Br J Clin Pharmacol 2018 Feb 21. Epub 2018 Feb 21.
    Cardiovascular and Metabolic Disease Innovative Medicine Unit, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
    Aims: AZD9977 is the first MR modulator in clinical development exerting similar organ protection as eplerenone with minimal urinary electrolyte effects in pre-clinical studies. The aim was to perform the initial clinical assessment of AZD9977.

    Methods: A first in man trial explored doses from 5-1200 mg. Read More

    Comparative cardiovascular safety of non-steroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study.
    Br J Clin Pharmacol 2018 Feb 22. Epub 2018 Feb 22.
    Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, 02215, USA.
    Aims: Prior studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. Few were active-comparison studies that directly assessed potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase-2 enzyme (COX-2) selective NSAIDs and nonselective NSAIDs in patients with hypertension. Read More

    Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation.
    Br J Clin Pharmacol 2018 Feb 19. Epub 2018 Feb 19.
    Laboratory of Clinical Pharmaceutics and Therapeutics, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga, 525-8577, Japan.
    Aims: This study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolising enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban.

    Methods: Data were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1, ABCG2, and CYP3A5 polymorphisms. Read More

    Impact of post-diagnostic statin use on ovarian cancer mortality: a systematic review and meta-analysis of observational studies.
    Br J Clin Pharmacol 2018 Feb 17. Epub 2018 Feb 17.
    Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
    Aim: To comprehensively evaluate the association between post-diagnostic statin use and mortality of ovarian cancer (OC) patients.

    Methods: Using a comprehensive strategy, multiple databases (Medline, Embase, and Web of Science) were systematically searched to identify observational studies that examined the correlation between statin use and OC mortality up to December 31, 2017. The studies were independently reviewed and selected based on predetermined selection criteria. Read More

    Intracellular pharmacokinetics of gemcitabine, its deaminated metabolite 2',2'-difluorodeoxyuridine and their nucleotides.
    Br J Clin Pharmacol 2018 Feb 16. Epub 2018 Feb 16.
    Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital - The Netherlands Cancer Institute and MC Slotervaart, Louwesweg 6, 1066, EC, Amsterdam, The Netherlands.
    Aims: Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) is a prodrug that has to be phosphorylated within the tumour cell to become active. Intracellularly formed gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) are held responsible for the antineoplastic effects. However, a major part of gemcitabine is converted into 2',2'-difluoro-2'-deoxyuridine (dFdU) by deamination. Read More

    Predictors of persistent prescription opioid analgesic use among people without cancer in Australia.
    Br J Clin Pharmacol 2018 Feb 16. Epub 2018 Feb 16.
    Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia.
    Aims: To identify patterns of opioid analgesic use and determine predictors of persistent opioid use among people without cancer.

    Methods: A population-based cohort study of Australians initiating prescription opioids from July 2013 to December 2015 was conducted using data from a random 10% sample of people who accessed medicines through Australia's Pharmaceutical Benefits Scheme. A 12-month look-back period was used to define opioid initiation, exclude people with cancer, and determine comorbidities. Read More

    Non-Commercial versus Commercial Clinical Trials: a Retrospective Study of the Applications Submitted to a Research Ethics Committee.
    Br J Clin Pharmacol 2018 Feb 15. Epub 2018 Feb 15.
    Clinical Pharmacology Service, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
    There are a lot of difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study some design characteristics, the clinical trial public register and the publication rate of non-commercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16. Read More

    Cerebrospinal Fluid Abacavir Concentrations in HIV-positive Patients Following Once-daily Administration.
    Br J Clin Pharmacol 2018 Feb 14. Epub 2018 Feb 14.
    Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
    Abacavir is a widely used nucleotide reverse transcriptase inhibitor whose cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and 9 HIV-positive once-daily and twice-daily abacavir intakers. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. Read More

    Marketing medicines: charting the rise of modern therapeutics through a systematic review of adverts in UK medical journals (1950-1980).
    Br J Clin Pharmacol 2018 Feb 14. Epub 2018 Feb 14.
    Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.
    Aims: To examine how pharmaceutical products that were first marketed between 1950 and 1980 were promoted to physicians through advertisements and briefly review advertising regulations and accuracy of the advertisements in the light of modern knowledge.

    Methods: We systematically reviewed advertisements promoting drugs for specific therapeutic areas, namely central nervous system disorders (anxiety and sleep disorders, depression, psychoses, and Parkinson's disease), respiratory disorders, cardiovascular disorders, and gastrointestinal disorders. We examined about 800 issues of the British Medical Journal (1950-1980) and about 150 issues of World Medicine (1965-84). Read More

    A descriptive systematic review of salivary TDM in neonates and infants.
    Br J Clin Pharmacol 2018 Feb 14. Epub 2018 Feb 14.
    Biomedical Sciences Research, Ulster University.
    Introduction: Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. Read More

    Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome.
    Br J Clin Pharmacol 2018 Feb 13. Epub 2018 Feb 13.
    Division of Nephrology, Dialysis, Transplantation, IRCCS Giannina Gaslini, Via Gerolamo Gaslini 5, Genoa, 16148, Italy.
    Aims: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin-inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed to consider repeated infusions. Read More

    Nutraceuticals: opening the debate for a regulatory framework.
    Br J Clin Pharmacol 2018 Feb 12. Epub 2018 Feb 12.
    Department of Pharmacy, University of Napoli Federico II, Via D. Montesano, 49 -, 80131, Naples, Italy.
    Currently, nutraceuticals do not have a specific definition distinct from those of other food-derived categories, such as food supplements, herbal products, pre- and probiotics, functional foods, and fortified foods. Many studies have led to an understanding of the potential mechanisms of action of pharmaceutically active components contained in food that may improve health and reduce the risk of pathological conditions while enhancing overall well-being. Nevertheless, there is a lack of clear information and, often, the claimed health benefits may not be properly substantiated by safety and efficacy information or in vitro and in vivo data, which can induce false expectations and miss the target for a product to be effective, as claimed. Read More

    Development of a nomogram for the estimation of long-term adherence to clozapine therapy using neutrophil fluorescence.
    Br J Clin Pharmacol 2018 Feb 9. Epub 2018 Feb 9.
    Department of Clinical Pharmacy, University Medical Center Utrecht, The Netherlands.
    Aims: Previously, we have reported an association between clozapine use and elevated FL3 neutrophil fluorescence, a flow-cytometric parameter for cell viability. Here, we developed and evaluated a PK/PD model relating FL3-fluorescence to clozapine exposure and derived a nomogram for estimation of long-term adherence.

    Methods: Data from 27 patients initiating clozapine were analyzed using non-linear mixed effects modelling. Read More

    Acenocoumarol As An Alternative Anticoagulant In A Patient With Warfarin Related Nephropathy.
    Br J Clin Pharmacol 2018 Feb 8. Epub 2018 Feb 8.
    Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
    Adverse Event: Warfarin related nephropathy DRUG IMPLICATED: Warfarin THE PATIENT: A 31 year old female, managed with warfarin for rheumatic heart disease with atrial fibrillation.

    Evidence That Links The Drug To The Event: There were no alternative causes of nephropathy that could have caused the adverse event in this patient.

    Management: Shifting the drug from warfarin to acenocoumarol MECHANISM, IF KNOWN: Difference in renal elimination between warfarin and acenocoumarol IMPLICATION FOR THERAPY: Clinicians should be aware of this rare adverse effect of warfarin and acenocoumarol can be considered as an alternative therapy for this condition. Read More

    Use of trimethoprim-sulfamethoxazole during pregnancy and risk of spontaneous abortion: a nested case control study.
    Br J Clin Pharmacol 2018 Feb 8. Epub 2018 Feb 8.
    Faculty of Pharmacy, University of Montreal, 2900 Edouard Montpetit, Montréal, (Québec), Canada, H3T 1J4.
    Aims: Data available on the fetal safety of trimethoprim-sulfamethoxazole exposure during pregnancy remains scarce and inconclusive. A previous study assessing the link between use TMP-SMX exposure during pregnancy and the risk of spontaneous abortion (SA) did not control for protopathic bias and indication bias.

    Methods: We conducted a nested control study (n= 77 429 pregnancies including 7039 cases of SA and 70 390 controls) within the Quebec Pregnancy Cohort. Read More

    Population pharmacokinetics of enoxaparin in early stage of pediatric liver transplantation.
    Br J Clin Pharmacol 2018 Feb 8. Epub 2018 Feb 8.
    EA7323, Evaluation des thérapeutiques et pharmacologie périnatale et pédiatrique, Université Paris Descartes, Paris, France.
    Aim: Preventing post liver transplantation (LT) hepatic artery and portal vein thrombosis includes enoxaparin administration. Enoxaparin pharmacokinetics (PK) has not been investigated in children following LT. We described an enoxaparin PK model in 22 children the first week following the LT. Read More

    Discontinuities and disruptions in drug dosage guidelines for the paediatric population.
    Br J Clin Pharmacol 2018 Feb 7. Epub 2018 Feb 7.
    Discipline of Pharmacology, Sydney Medical School, Translational Australian Clinical Toxicology Program, The University of Sydney, NSW, Australia, 2006.
    Aims: This study investigates paediatric drug dosage guidelines with the aim of investigating their agreement with body surface area (BSA) scaling principles.

    Methods: A total of 454 drug dosage guidelines listed in the AMH-CDC 2015 were examined. Data extracted included the administration, frequency and dose per age bracket from 0 to 18 years. Read More

    Effects of training physicians in electronic prescribing in the outpatient setting on clinical, learning and behavioural outcomes, a cluster randomized trial.
    Br J Clin Pharmacol 2018 Feb 4. Epub 2018 Feb 4.
    Department of Internal Medicine & Centre for Research and Development of Education, University Medical Centre Utrecht, The Netherlands.
    Aims: Electronic prescribing systems may improve medication safety, but only when used appropriately. Effects of a task-analysis based training were evaluated in the outpatient setting on clinical, learning and behavioral outcomes, compared with usual educational approach.

    Methods: Multicenter, cluster-randomized trial (MEDUCATE trial) with physicians as unit of analysis. Read More

    Threats to global antimicrobial resistance control: Centrally approved and unapproved antibiotic formulations sold in India.
    Br J Clin Pharmacol 2018 Feb 4. Epub 2018 Feb 4.
    Institute of Health and Society, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK.
    Aims: Rising antimicrobial resistance (AMR) is a global health crisis. India has among the highest resistance rates and antibiotic consumption internationally. Extensive use of fixed-dose combination (FDC) antibiotics and of unapproved formulations are claimed contributory factors but there has been no systematic examination of formulations or volumes sold. Read More

    The pharmacodynamic and clinical trial evidence for statin dose.
    Br J Clin Pharmacol 2018 Feb 2. Epub 2018 Feb 2.
    Medicines Assessment Ltd, 196 Rotherhithe St, London, SE16 7RB, UK.
    Statin doses around estimated effective dose 50 (ED50) can reduce myocardial infarction by over 25% and mortality by around 10%. Being a competitive enzyme inhibitor, statin efficacy plateaus at doses that are multiples above the ED50, whilst on- and off-target adverse events increase in number and severity with increasing dose. For example, myopathy has been shown to increase by up to 29-fold and liver dysfunction by up to 9-fold as statin dose is increased. Read More

    Argon attenuates multiorgan failure following experimental aortic cross-clamping.
    Br J Clin Pharmacol 2018 Jan 31. Epub 2018 Jan 31.
    Inserm, U955, Equipe 3, Créteil, France.
    Aims: Argon was shown to prevent ischemic injuries in several situations of regional ischemia. We determined whether it could provide a systemic effect in a model of multiorgan failure (MOF) induced by aortic cross-clamping.

    Methods: Anesthetized rabbits were submitted to aortic cross-clamping (30 min) and subsequent reperfusion (300 min). Read More

    GSH-PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first-in-human study.
    Br J Clin Pharmacol 2018 Jan 31. Epub 2018 Jan 31.
    Centre for Human Drug Research, Leiden, the Netherlands.
    Aim: Intravenous high-dose free methylprednisolone hemisuccinate (MP) is the primary treatment for an acute relapse in relapsing-remitting (RR) multiple sclerosis (MS). However, it is inconvenient and its side effects are undesirable. Both dose and dosing frequency can be reduced by incorporating free MP in glutathione (GSH) PEGylated liposomes, creating a slow-release formulation with reduced toxicity and prolonged peripheral efficacy. Read More

    A clinically relevant decrease in abiraterone exposure associated with carbamazepine use in a patient with castration-resistant metastatic prostate cancer.
    Br J Clin Pharmacol 2018 Jan 31. Epub 2018 Jan 31.
    Department of Medical Oncology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
    Adverse Event: Decreased abiraterone exposure after introducing carbamazepine.

    Drugs Implicated: Abiraterone acetate and carbamazepine.

    The Patient: A 65-year-old man with metastatic castration resistant prostate cancer, was treated with abiraterone acetate and prednisolone, and received concomitant carbamazepine for treatment of facial neuropathy. Read More

    The effect of itraconazole and rifampicin on the pharmacokinetics of osimertinib.
    Br J Clin Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Winship Cancer Institute of Emory University, Atlanta, GA, USA.
    Aims: We investigated the effects of a strong CYP3A4 inhibitor (itraconazole) or inducer (rifampicin) on the pharmacokinetics of the epidermal growth factor receptor kinase inhibitor osimertinib, in patients with advanced non-small cell lung cancer in two phase I, open-label, two-part clinical studies. Part one of both studies is reported.

    Methods: In the itraconazole study (NCT02157883), patients received single-dose osimertinib 80 mg on Days 1 and 10 and itraconazole (200 mg twice daily) on Days 6-18 orally. Read More

    Ticagrelor attenuates myocardial ischemia-reperfusion injury possibly through downregulating galectin-3 expression in the infarct area of rats.
    Br J Clin Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Department of Cardiology, Puai Hospital, Huazhong University of Science and Technology, Wuhan, 430033, China.
    Aims: The full benefits of myocardial revascularization strategies applied to acute myocardial infarction patients might be reduced by myocardial ischemia and reperfusion (I/R) injury. It is known that inflammation plays an important role in the pathogenesis of I/R injury and galectin-3, a known inflammatory factor, is actively involved in ischemia-induced inflammation and fibrosis of various organs. Previous studies demonstrated that anti-platelets therapy with ticagrelor, a new P2Y12 receptor antagonist, could effectively attenuate myocardial I/R injury and I/R injury related inflammatory responses. Read More

    Balancing early access with uncertainties in evidence for drugs authorized by prospective case series - systematic review of reimbursement decisions.
    Br J Clin Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Aims: To review clinical and cost-effectiveness evidence underlying reimbursement decisions relating to drugs whose authorization mainly is based on evidence from prospective case series.

    Methods: A systematic review of all new drugs evaluated in 2011-2016 within a health care profession-driven resource prioritization process, with a market approval based on prospective case series, and a reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Board (TLV). Public assessment reports (EPARs) from the European Medicines Agency (EMA), published pivotal studies, and TLV, Scottish Medicines Consortium (SMC) and National Institute of Health and Care Excellence (NICE) decisions and guidance documents were reviewed. Read More

    Time-to-event modelling of effect of codrituzumab on overall survival in patients with hepatocellular carcinoma.
    Br J Clin Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Translational and Clinical Research Center, Hoffmann-La Roche Inc., New York City, USA.
    Aims: Codrituzumab (GC33) is a recombinant, humanized mAb that binds to glypican-3 (GPC3), an oncofoetal protein highly expressed in hepatocellular carcinoma (HCC). This investigation aimed to identify clinically relevant factors that may affect the overall survival (OS) in HCC patients treated with codrituzumab and to quantitatively annotate their effects.

    Methods: Codrituzumab exposure was estimated by a population pharmacokinetics model with a non-linear elimination pathway. Read More

    Implications of inter-correlation between hepatic CYP3A4-CYP2C8 enzymes for the evaluation of drug-drug interactions: a case study with repaglinide.
    Br J Clin Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Centre for Applied Pharmacokinetic Research, Division of Pharmacy & Optometry, University of Manchester, Manchester, UK.
    Aims: Statistically significant positive correlations are reported for the abundance of hepatic drug-metabolising enzymes. We investigate, as an example, the impact of CYP3A4-CYP2C8 inter-correlation on the predicted inter-individual variabilities of clearance and drug-drug interactions (DDIs) for repaglinide using physiologically-based pharmacokinetic (PBPK) modelling.

    Methods: PBPK modelling and simulation was employed using Simcyp Simulator (v15. Read More

    Integrating data from the IMPD/IB. A new tool for translational integration of preclinical effects.
    Br J Clin Pharmacol 2018 Jan 30. Epub 2018 Jan 30.
    Centre for Human Drug Research, Zernikedreef 8, 2333 CL, Leiden, The Netherlands.
    The first administration of a new compound in humans is an important milestone. A major source of information for the researcher is the 'investigator's brochure' (IB). Such a document, has a size of several hundred pages. Read More

    Exposure-response characterisation of tofacitinib efficacy in moderate to severe ulcerative colitis: results from a dose-ranging phase 2 trial.
    Br J Clin Pharmacol 2018 Jan 28. Epub 2018 Jan 28.
    Pfizer Inc, Collegeville, PA, USA.
    Background And Aims: Tofacitinib is an oral, small molecule JAK inhibitor being investigated for UC. In a phase 2 dose-ranging study, tofacitinib demonstrated efficacy vs placebo as UC induction therapy. In this post-hoc analysis, we aimed to compare tofacitinib dose and plasma concentration as predictors of efficacy and identify covariates that determined efficacy in patients with UC. Read More

    Developmental pharmacogenetics of CYP2C19 in neonates and young infants: omeprazole as a probe drug.
    Br J Clin Pharmacol 2018 Jan 28. Epub 2018 Jan 28.
    Department of Paediatric Pharmacology and Pharmacogenetics, Robert Debré University Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
    Background: Although substantial progress has been made in understanding of ontogeny of drug metabolism, there is still a gap of knowledge in developmental pharmacogenetics in neonates. We hypothesized that both age and pharmacogenetics might explain the developmental pattern of CYP2C19. We conducted a population pharmacokinetic-pharmacogenetic study to quantify the developmental pharmacogenetics of CYP2C19 in neonates and young infants using omeprazole as a probe drug. Read More

    The impact of parallel regulatory-HTA scientific advice on clinical development. Assessing the uptake of regulatory and HTA recommendations.
    Br J Clin Pharmacol 2018 Jan 25. Epub 2018 Jan 25.
    European Medicines Agency (EMA), 30 Churchill Place, London, E14 5EU, United Kingdom.
    Background: The "Parallel regulatory-HTA SA" (PSA) procedure allows manufacturers to receive simultaneous feedback from both EU regulators and HTA bodies on development plans for new medicines.

    Objectives: Primary objective of the present study is to investigate whether PSA is integrated in the clinical development programmes for which advice was sought.

    Methods: Contents of PSA provided by regulators and HTA bodies for each procedure between 2010 and 2015 were analysed. Read More

    Critical evaluation of causality assessment of herb-drug interactions in patients.
    Br J Clin Pharmacol 2018 Jan 24. Epub 2018 Jan 24.
    Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Tygerberg, 7505, South Africa.
    The aim of this review was to assess the severity of adverse drug reactions (ADRs) due to herb-drug interactions (HDI) in patients taking herbs and prescribed medications based on published evidence. Electronic databases of PubMed, the Cochrane Library, Medline and Scopus were searched for randomized or nonrandomized clinical studies, case-control and case reports of HDI. The data were extracted and the causal relationship of ADRs as consequences of HDI assessed using Horn's drug interaction probability scale or Roussel Uclaf Causality Assessment Method scoring systems. Read More

    Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations.
    Br J Clin Pharmacol 2018 Jan 19. Epub 2018 Jan 19.
    Infectious Diseases and Clinical Pharmacology Units, The Royal Childrenaposs Hospital Melbourne, Parkville, Victoria, Australia.
    Aim: Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin-B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children. Read More

    Br J Clin Pharmacol 2018 Jan 20. Epub 2018 Jan 20.
    Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro.
    Aim: To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort.

    Methods: The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry. Read More

    Drug promotion practices: A review.
    Br J Clin Pharmacol 2018 Jan 18. Epub 2018 Jan 18.
    Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India.
    Over the years, the pharmaceutical industry has been at the forefront of research and innovation in drug discovery and development. The process of drug discovery extending from preclinical studies to multicentric clinical trials and postmarketing phase is a costly affair running into billions of dollars. On the flip side, not all investigational molecules clear the trial phases and get approved, which puts pressure on the manufacturers to maximize the profit from approved drugs. Read More

    First in human study to assess safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects.
    Br J Clin Pharmacol 2018 Jan 18. Epub 2018 Jan 18.
    Early Clinical and Translational Research, Bristol-Myers Squibb Company, Princeton, NJ, 08540.
    Aims: To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects.

    Methods: This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1. Read More

    Clinical impact of pharmacokinetic interactions between the HCV protease inhibitor simeprevir and frequently used concomitant medications.
    Br J Clin Pharmacol 2018 Jan 18. Epub 2018 Jan 18.
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
    Aims: Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C (HCV) can be associated with drug-drug interactions (DDIs) with concomitant medications. The practical clinical implications of such DDIs are poorly understood. We assessed the clinical impact of possible pharmacokinetic (PK) interactions between simeprevir and frequently prescribed concomitant medications. Read More

    Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs.
    Br J Clin Pharmacol 2018 Jan 16. Epub 2018 Jan 16.
    Eisai, Inc., Woodcliff Lake, NJ, USA.
    Aims: Avatrombopag, a thrombopoietin receptor agonist, is a substrate of cytochrome P450 (CYP) 2C9 and CYP3A. We assessed three drug-drug interactions of avatrombopag as a victim with dual or selective CYP2C9/3A inhibitors and inducers.

    Methods: This was a three-part, open-label study. Read More

    The impact of diuretic use and ABCG2 genotype on the predictive performance of a published allopurinol dosing tool.
    Br J Clin Pharmacol 2018 Jan 17. Epub 2018 Jan 17.
    Department of Medicine, University of Otago, Christchurch, New Zealand.
    Aim: This research aims to evaluate the predictive performance of a published allopurinol dosing tool.

    Methods: Allopurinol dose predictions were compared to the actual dose required to achieve serum urate (SU) <0.36 mmol lusing mean prediction error. Read More

    Better characterization of vinflunine pharmacokinetics variability and exposure/toxicity relationship to improve its use: analyses from 18 trials.
    Br J Clin Pharmacol 2018 Jan 17. Epub 2018 Jan 17.
    Institut de Recherche Pierre Fabre, Toulouse, France.
    Aims: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. Read More

    Rhabdomyolysis after co-administration of a statin and fusidic acid: an analysis of the literature and of the WHO database of adverse drug reactions.
    Br J Clin Pharmacol 2018 Jan 16. Epub 2018 Jan 16.
    Regional Pharmacovigilance Centre, Department of Medical Pharmacology, CHU Bordeaux, F-33000, Bordeaux, France.
    Following a severe case of rhabdomyolysis in our University Hospital after a co-administration of atorvastatin and fusidic acid, we describe this interaction as this combination is not clearly contraindicated in some countries, particularly for long-term treatment by fusidic acid. All cases of rhabdomyolysis during a co-administration of a statin and fusidic acid were identified in the literature and in the World and Health Organization database, VigiBase®. In the literature, 29 cases of rhabdomyolysis were identified; mean age was 66 years, median duration of co-administration before rhabdomyolysis occurrence was 21 days, 28% of cases were fatal. Read More

    Systematic review of predictive risk models for adverse drug events in hospitalized patients.
    Br J Clin Pharmacol 2018 Jan 16. Epub 2018 Jan 16.
    School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, QLD, 4102, Australia.
    Aim: An emerging approach to reducing hospital adverse drug events is the use of predictive risk scores. The aim of this systematic review was to critically appraise models developed for predicting adverse drug event risk in inpatients.

    Methods: Embase, PubMed, CINAHL and Scopus databases were used to identify studies of predictive risk models for hospitalized adult inpatients. Read More

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