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    10906 results match your criteria British journal of clinical pharmacology[Journal]

    1 OF 219

    Adverse Effects of a Single Dose of Gentamicin in Adults: A Systematic Review.
    Br J Clin Pharmacol 2017 Sep 21. Epub 2017 Sep 21.
    Whittall Street Clinic, University Hospitals Birmingham NHS Trust, Birmingham, B4 6DH, UK.
    Aim: Systematically review the frequency and type of adverse events associated with a single dose of intravenous or intramuscular gentamicin in adults, for any indication, in studies where a comparator was available.

    Methods: A review protocol was developed and registered (PROSPERO: CRD42013003229). Studies were eligible for review if they; recruited participants ≥16 years old, used gentamicin intramuscularly or intravenously as a single one-off dose, compared gentamicin to another medication or placebo, and if adverse events were monitored. Read More

    Quantitative analysis of the effect of end-tidal carbon dioxide on regional cerebral oxygen saturation in patients undergoing carotid endarterectomy under general anaesthesia.
    Br J Clin Pharmacol 2017 Sep 23. Epub 2017 Sep 23.
    Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
    Aim: Regional cerebral oxygen saturation (rSO2 ) is currently the most used measure in clinical practice to monitor cerebral ischemia in patients undergoing carotid endarterectomy (CEA). Although end-tidal carbon dioxide (PET CO2 ) is known as a factor that influences rSO2 , the relationship between PET CO2 and rSO2 has not been quantitatively evaluated in patients with severe arteriosclerosis. This study aimed to evaluate the effect of PET CO2 on rSO2 in patients undergoing CEA under general anaesthesia. Read More

    Protective, repairing and fibrinolytic effects of rivaroxaban on vascular endothelium.
    Br J Clin Pharmacol 2017 Sep 23. Epub 2017 Sep 23.
    Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Travesía da Choupana s/n, Santiago de Compostela, 15706, A Coruña, Spain.
    Aim: Rivaroxaban, a direct inhibitor of activated factor X (FXa), is the only new oral anticoagulant approved for secondary prevention after acute coronary syndrome. Our objective was to identify the possible molecular mechanisms of rivaroxaban that contributes to endothelial function.

    Methods: Cell viability and growth of human umbilical vein endothelial cells (HUVEC) were registered. Read More

    Safety, tolerability, and pharmacokinetics of radavirsen (AVI-7100), an antisense oligonucleotide targeting influenza a M1/M2 translation.
    Br J Clin Pharmacol 2017 Sep 20. Epub 2017 Sep 20.
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
    Aims: The aims of the present study were to assess the safety, tolerability and pharmacokinetics of radavirsen following single ascending doses and multiple doses given as intravenous infusions in healthy adults.

    Methods: A phase I safety and pharmacokinetic study of radavirsen was performed in healthy volunteers. The study was divided into two parts. Read More

    Inclusion of pregnant and breastfeeding women in research - Efforts and Initiatives.
    Br J Clin Pharmacol 2017 Sep 19. Epub 2017 Sep 19.
    Obstetric and Pediatric Pharmacology and Therapeutics Branch at NICHD.
    Pregnant and breastfeeding women have been rendered therapeutic orphans as they have been historically excluded from clinical trials. Labeling for most approved drugs does not provide information about safety and efficacy during pregnancy. This lack of data is mainly due to ethico-legal challenges that have remained entrenched in the post-diethylstilbestrol and thalidomide era, and that have led to pregnancy being viewed in the clinical trial setting primarily through a pharmacovigilance lens. Read More

    Pharmacodynamics and Pharmacokinetics of Ticagrelor Versus Clopidogrel in Patients with Acute Coronary Syndromes and Chronic Kidney Disease.
    Br J Clin Pharmacol 2017 Sep 15. Epub 2017 Sep 15.
    General Hospital of Shenyang Military Region, Shenyang, China.
    Background: Pivotal clinical trials found ticagrelor reduced ischemic complications to a greater extent than clopidogrel and what is more, the benefit gradually increased with the reduction on creatinine clearance. However, the underlying mechanisms remains poorly explored.

    Methods: This is a single-center, prospective, randomized clinical trial involving 60 hospitalized P2Y12 inhibitor naïve patients with CKD (eGFR<60ml/min/1. Read More

    Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.
    Br J Clin Pharmacol 2017 Sep 13. Epub 2017 Sep 13.
    The University of Liverpool, The Wolfson Centre for Personalised Medicine, Block A: Waterhouse Buildings, 1-5 Brownlow Street, Liverpool, L69 3GL.
    The second most common cause of hospitalisation due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalisation. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Read More

    External Evaluation of Population Pharmacokinetic Models for Cyclosporine in Adult Renal Transplant Recipients.
    Br J Clin Pharmacol 2017 Sep 11. Epub 2017 Sep 11.
    Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.
    Aim: Several population pharmacokinetic (popPK) models for cyclosporine (CsA) in adult renal transplant recipients have been constructed to optimise the therapeutic regimen of CsA. However, little is known about their predictabilities when extrapolated to different clinical centres. Therefore, this study aimed to externally evaluate the predictive ability of CsA popPK models and determine the potential influencing factors. Read More

    Co-administration of cyclosporine and ticagrelor may lead to a higher exposure to cyclosporine: a case report of a 49-year old man.
    Br J Clin Pharmacol 2017 Sep 11. Epub 2017 Sep 11.
    Department of Internal Medicine, Máxima Medical Center, Veldhoven, the Netherlands.
    Adverse Event: A drug interaction leading to higher exposure to cyclosporine DRUGS IMPLICATED: Cyclosporine and ticagrelor THE PATIENT: A 49-year old man with a stable renal graft, managed with cyclosporine with stable trough blood concentrations for several years, was treated with ticagrelor for unstable angina pectoris EVIDENCE THAT LINKS THE DRUG TO THE EVENT: The timeline was consistent with the appearance of an interaction, the interaction was confirmed by an increase in trough concentration of cyclosporine, and there were no alternative causes that by themselves could have caused the increase in cyclosporine exposure MANAGEMENT: Cessation of ticagrelor MECHANISM: Inhibition of CYP3A4 and P-glycoprotein by ticagrelor IMPLICATIONS FOR THERAPY: Clinicians should be aware of this potential interaction as ticagrelor is frequently prescribed in individuals using cyclosporine. Close monitoring of cyclosporine serum concentrations is warranted to avoid overdosing of cyclosporine. A pharmacokinetic study is needed to further examine the probable interaction between cyclosporine and ticagrelor. Read More

    Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: Rationale for lower dosage in Asia.
    Br J Clin Pharmacol 2017 Sep 11. Epub 2017 Sep 11.
    Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
    Aims: This population pharmacokinetic analysis was conducted to quantitatively describe the regional differences and sources of inter-patient variability on the apparent oral clearance of alisertib.

    Methods: A population pharmacokinetic analysis was performed on data from 671 cancer patients in Western countries and in Japan/ East Asia administered alisertib 5-150 mg once or twice daily in multiple dosing schedules. The final model was used to simulate alisertib pharmacokinetics in patients in the West and East Asian regions in the single agent schedule of 7 days of dosing in a 21 day cycle. Read More

    Pharmacokinetics of multiple doses of Co-Crystal of Tramadol-Celecoxib: findings from a 4-way randomized open-label Phase I clinical trial.
    Br J Clin Pharmacol 2017 Sep 9. Epub 2017 Sep 9.
    Laboratorios del Dr. Esteve, S.A.U., Barcelona, Spain.
    Aim: We compared the pharmacokinetic (PK) profiles of Co-Crystal of Tramadol-Celecoxib (CTC) versus each reference product (alone and in open combination) after single (first dose) and multiple dosing.

    Methods: Healthy adults aged 18-50 years received, under fasted conditions, 15 twice-daily doses of the following treatments (separated by ≥14-day wash-out): 200 mg immediate-release (IR) CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment-1); 100 mg IR tramadol (Treatment-2), 100 mg celecoxib (Treatment-3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment-4). Treatment sequence was assigned by computer-generated randomization. Read More

    Factor Xa inhibition by rivaroxaban in the trough steady state can significantly reduce thrombin generation.
    Br J Clin Pharmacol 2017 Sep 9. Epub 2017 Sep 9.
    Department of Cardiology and Nephrology, Dokkyo Medical University, Tochigi, Japan.
    Aims: The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration.

    Methods: A single-centre, prospective, non-randomised, drug intervention, self-controlled study was conducted in 51 anticoagulation therapy-naïve patients with non-valvular atrial fibrillation. Plasma rivaroxaban concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and anti-factor Xa chromogenic assay. Read More

    Impact of non-adherence on the safety and efficacy of uric acid lowering therapies in the treatment of gout.
    Br J Clin Pharmacol 2017 Sep 9. Epub 2017 Sep 9.
    Centre for Health Economic and Medicines Evaluation, Bangor University.
    Aims: Dual-urate lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosurics can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of this study were to simulate the relation between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono and dual-ULTs. Read More

    Hydroxycarbamide in Children with Sickle Cell Anemia After First-dose Vs. Chronic Therapy: Pharmacokinetics and Predictive Models for Drug Exposure.
    Br J Clin Pharmacol 2017 Sep 8. Epub 2017 Sep 8.
    Department of Pediatrics, Section of Clinical Pharmacology and Medical Toxicology, Arkansas Children's Hospital, Little Rock, AR, USA.
    Aims: The purpose of this work was to (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HCnew ) versus those receiving chronic therapy (HCchronic ), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies based on a limited number of HC measurements.

    Methods: Utilizing data from two prospective, multicenter trials of hydroxycarbamide (Pharmacokinetics of Liquid Hydroxyurea in Pediatric Patients with Sickle Cell Anemia; NCT01506544 and Single-Dose (SD) and Steady-State (SS) Pharmacokinetics of Hydroxyurea in Children and Adolescents with Sickle Cell Disease), plasma drug concentration versus time profiles were evaluated with a model independent approach in the HCnew and HCchronic groups. Various predictive senerios were analyzed to evaluate if systemic exposure with hydroxycarbamide could be accurately predicted. Read More

    Drug-drug interaction potential in men treated with enzalutamide: Mind the gap.
    Br J Clin Pharmacol 2017 Sep 7. Epub 2017 Sep 7.
    Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
    Aim: Metastatic castration resistant prostate cancer (mCRPC) patients are generally older patients with several co-morbidities and are therefore more at risk for complications due to drug-drug interactions(DDIs). We assessed the prevalence of potential DDIs in a cohort of mCRPC patients treated with enzalutamide.

    Methods: We conducted a retrospective review of pharmacy records to retrieve individual drug histories of mCRPC patients who started enzalutamide therapy in a tertiary care setting. Read More

    Urinary miR-155-5p and CXCL10 as prognostic and predictive biomarkers of rejection, graft outcome and treatment response in kidney transplantation.
    Br J Clin Pharmacol 2017 Sep 7. Epub 2017 Sep 7.
    Pharmacology and Toxicology Laboratory, CDB, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Spain.
    Aims: MicroRNAs (miRNAs) may be useful biomarkers of rejection and allograft outcome in kidney transplantation. Elevated urinary CXCL10 levels have been associated with acute rejection (AR) and may predict allograft failure. We examined the correlation of miRNA, CXCL10 levels and immunosuppressive drug exposure with AR and graft function in kidney transplant recipients. Read More

    Biomarkers in solid organ transplantation.
    Br J Clin Pharmacol 2017 Sep 7. Epub 2017 Sep 7.
    Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
    Recipients of solid organs such as the kidney and heart are treated with standard immunosuppressive regimens, and personalized medicine has not yet reached the clinic for this patient population. Biomarkers potentially will allow treatment regimens to be adjusted, according to the needs of the individual patient. Biomarkers may reflect the degree of immunosuppression of the immune system, or they may reflect early damage to the transplanted organ. Read More

    Dose-dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor.
    Br J Clin Pharmacol 2017 Sep 2. Epub 2017 Sep 2.
    Eli Lilly and Company, Lilly Corporate Center, 893 South Delaware Street, Indianapolis, Indiana, USA.
    Aim: LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety, and tolerability profile.

    Methods: Healthy subjects were randomised to receive LY3031207 (25, 75, and 275 mg), placebo, or celecoxib (400 mg) once daily for 28 days. The safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated. Read More

    Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours.
    Br J Clin Pharmacol 2017 Sep 2. Epub 2017 Sep 2.
    Daiichi Sankyo, Inc., Edison, New Jersey, USA.
    Aim: This phase 1, open-label, crossover study sought to evaluate drug-drug interactions between tivantinib and cytochrome P450 (CYP) substrates and tivantinib and P-glycoprotein.

    Methods: The effect of tivantinib doses on the pharmacokinetics of the probe drugs for CYP1A2 (caffeine), CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (midazolam), and for P-glycoprotein (digoxin) was investigated in 28 patients with advanced cancer using a cocktail probe approach. Patients received single doses of probe drugs alone and after 5 days of treatment with tivantinib 360 mg twice daily. Read More

    Clinical significance of CYP2C19 polymorphisms on the metabolism and pharmacokinetics of 11β-hydroxysteroid dehydrogenase type-1 inhibitor BMS-823778.
    Br J Clin Pharmacol 2017 Aug 29. Epub 2017 Aug 29.
    Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, NJ, 08543.
    Aims: BMS-823778 is an inhibitor of 11β-hydroxysteroid dehydrogenase type-1, thus a potential candidate for Type 2 diabetes treatment. Here, we investigated the metabolism and pharmacokinetics of BMS-823778 to understand its pharmacokinetic variations in early clinical trials.

    Methods: The metabolism of BMS-823778 was characterized in multiple in vitro assays. Read More

    Non-cholestatic acute hepatitis following Candesartan administration.
    Br J Clin Pharmacol 2017 Aug 25. Epub 2017 Aug 25.
    Escuela de Medicina, Tecnologico de Monterrey.
    Arterial hypertension is nowadays a highly manageable disorder due to a variety of drugs available for its treatment. Since the late 1990's, angiotensin II receptor blockers have been widely prescribed, achieving appropriate control in patients' blood pressure. Few cases of serious adverse effects have been reported to date. Read More

    Population pharmacokinetics of the MEK inhibitor selumetinib and its active N-desmethyl metabolite: data from 10 phase I trials.
    Br J Clin Pharmacol 2017 Aug 23. Epub 2017 Aug 23.
    AstraZeneca, Waltham, MA, USA.
    Aims: The aims of the study were to characterize the pharmacokinetics (PK) of selumetinib (AZD6244; ARRY-142886), a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor in clinical development for various indications, and its N-desmethyl metabolite in healthy volunteers, and evaluate clinically important covariates.

    Methods: A pooled-population PK analysis was performed using a nonlinear mixed-effects approach with plasma concentration data from 346 subjects who received single oral doses of selumetinib 20-75 mg across 10 phase I studies. Absolute bioavailability was determined using intravenous [(14) C] selumetinib. Read More

    Population Pharmacokinetic Meta-Analysis of Ramucirumab in Cancer Patients.
    Br J Clin Pharmacol 2017 Aug 18. Epub 2017 Aug 18.
    Eli Lilly and Company, Indianapolis, Indiana, USA.
    Aim: Ramucirumab is a human IgG1 monoclonal antibody that specifically binds vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks binding of VEGF-A, VEGF-C, and VEGF-D. The objective of the analysis was to characterize the clinical pharmacology profile of ramucirumab using a population pharmacokinetic approach.

    Methods: A total of 1639 patients with 6427 serum concentrations from 11 Phase 1b, 2, and 3 clinical trials in patients with various cancer indications were included in the analysis. Read More

    Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children.
    Br J Clin Pharmacol 2017 Aug 16. Epub 2017 Aug 16.
    Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park, UK.
    Aim: Population pharmacokinetic modelling has been widely used across many therapeutic areas to identify sources of variability, which are incorporated into models as covariate factors. Despite numerous publications on pharmacokinetic (PK) drug-drug interactions (DDIs) between antiepileptic drugs (AEDs), such data are not used to support the dose rationale for polytherapy in the treatment of epileptic seizures. Here we assess the impact of DDIs on plasma concentrations and evaluate the need for AED dose adjustment. Read More

    Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial.
    Br J Clin Pharmacol 2017 Aug 17. Epub 2017 Aug 17.
    Department of Nephrology & Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
    Introduction: Hypertension is only controlled in approximately 35% of the patients, which could be partially due to non-adherence. Recently, bioanalytical assessment of adherence to blood pressure (BP) lowering drugs has gaining interest. Our aim was to explore possible determinants of non-adherence in treatment resistant hypertension, assessed by objective screening for antihypertensive agents in serum. Read More

    Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects.
    Br J Clin Pharmacol 2017 Aug 15. Epub 2017 Aug 15.
    Laboratorios del Dr. Esteve, S.A.U., Barcelona, Spain.
    Aims: Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination.

    Methods: Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Read More

    Therapeutic drug monitoring of voriconazole for treatment and prophylaxis of invasive fungal infection in children.
    Br J Clin Pharmacol 2017 Aug 14. Epub 2017 Aug 14.
    Department of Medical Sciences, University of Turin - ASL "Città di Torino", Laboratory of Clinical Pharmacology and Pharmacogenetics*, Amedeo di Savoia Hospital, Turin, Italy.
    Voriconazole therapeutic drug monitoring is not consistently recommended due to its high interpatient and intrapatient variability. Here, we aimed to describe our experience with voriconazole for treatment and prophylaxis of invasive fungal infections in paediatric patients. A fully validated high-performance liquid chromatography-mass spectrometry method was used to quantify voriconazole concentration in plasma, at the end of dosing interval. Read More

    In vivo and in vitro palatability testing of a new paediatric formulation of valaciclovir.
    Br J Clin Pharmacol 2017 Aug 11. Epub 2017 Aug 11.
    Institute of Medical Sciences, Infection, Immunity and Inflammation Research Group; Aberdeen Fungal Group, University of Aberdeen, UK.
    Aims: The palatability of a new paediatric formulation of valaciclovir was assessed in children and their parents: non-inferiority of the new paediatric formulation (test formulation) compared to the reference formulation was investigated.

    Methods: In vivo palatability testing was performed in a randomized, two-period, multicentre, cross-over study. Children and their parents scored the liking of the new paediatric valaciclovir formulation and the reference formulation on a 100 mm visual analogue scale (VAS). Read More

    Epithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).
    Br J Clin Pharmacol 2017 Aug 11. Epub 2017 Aug 11.
    Respiratory Therapy Area Unit, GSK R&D, King of Prussia, Pennsylvania, USA.
    Aims: Cathepsin C (CTSC) is necessary for the activation of several serine proteases including neutrophil elastase (NE), cathepsin G and proteinase 3. GSK2793660 is an oral, irreversible inhibitor of CTSC that is hypothesized to provide an alternative route to achieve NE inhibition and was tested in a Phase I study.

    Methods: Single escalating oral doses of GSK2793660 from 0. Read More

    Suboptimal cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines.
    Br J Clin Pharmacol 2017 Aug 11. Epub 2017 Aug 11.
    Paris Descartes University, EA 7323, Paris, France.
    Aims: A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole [sulfamethoxazole (SMX) and trimethoprim (TMP)] advised by the WHO.

    Methods: Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/40 mg of TMP once daily). A nonlinear mixed effects modelling approach was used to analyse plasma concentrations. Read More

    The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC-Trial): A randomized controlled first-in-human trial.
    Br J Clin Pharmacol 2017 Aug 10. Epub 2017 Aug 10.
    Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
    Aims: Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. Read More

    Dried blood spots from finger prick facilitate therapeutic drug monitoring of adalimumab and anti-adalimumab in patients with inflammatory diseases.
    Br J Clin Pharmacol 2017 Aug 9. Epub 2017 Aug 9.
    Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands.
    Aims: Development of a self-sampling method for therapeutic drug monitoring (TDM) of biologicals will enhance TDM implementation in routine care and pharmacokinetic knowledge. The aim of this study was to compare adalimumab and anti-adalimumab antibody (ADA) concentration measurements in dried blood spots (DBS) obtained from finger prick with measurements in serum obtained via venepuncture, from patients with rheumatic inflammatory diseases.

    Methods: In this cross-sectional study, 161 consecutive patients were included. Read More

    Unlicensed and off-label uses of medicines: definitions and clarification of terminology.
    Br J Clin Pharmacol 2017 Aug 5. Epub 2017 Aug 5.
    West Midlands Centre for Adverse Drug Reactions, City Hospital, B18 7QH, UK.
    The terms "licensed", "unlicensed", and "off-label", often used in relation to marketing and prescribing medicinal products, may confuse UK prescribers. To markset a medicinal product in the UK requires a Marketing Authorisation ("product licence") for specified indications under specified conditions, regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). The Marketing Authorisation includes the product's agreed terms of use (the "label"), described in the Summary of Product Characteristics (SmPC). Read More

    Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children.
    Br J Clin Pharmacol 2017 Aug 3. Epub 2017 Aug 3.
    INSERM U1129, Paris, France.
    Aims: Oxcarbazepine is an antiepileptic drug with an activity mostly due to its monohydroxy derivative metabolite (MHD). A parent-metabolite population pharmacokinetic model in children was developed to evaluate the consistency between the recommended paediatric doses and the reference range for trough concentration (Ctrough ) of MHD (3-35 mg l(-1) ).

    Methods: A total of 279 plasma samples were obtained from 31 epileptic children (age 2-12 years) after a single dose of oxcarbazepine. Read More

    Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.
    Br J Clin Pharmacol 2017 Aug 3. Epub 2017 Aug 3.
    Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    Aims: Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. Read More

    Renal toxicity and chemotherapy in children with cancer.
    Br J Clin Pharmacol 2017 Jul 31. Epub 2017 Jul 31.
    Division of Paediatric Oncology, Catholic University of Rome, Rome, Italy.
    The clinical use of antineoplastic drugs can be limited by different drug-induced toxicities. Of these, renal dysfunction may be one of the most troublesome in that it can be cumulative and in general is only partially reversible with the discontinuation of the treatment. Renal toxicity may be manifested as a reduction of the glomerular filtration rate, electrolyte imbalances, or acute renal failure. Read More

    Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.
    Br J Clin Pharmacol 2017 Jul 31. Epub 2017 Jul 31.
    Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
    Aims: To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard.

    Methods: Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Read More

    Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation.
    Br J Clin Pharmacol 2017 Jul 23. Epub 2017 Jul 23.
    Medical Research Laboratory, Aarhus University, Aarhus, Denmark.
    Aims: The nicotinic acid analogue acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. Read More

    FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms.
    Br J Clin Pharmacol 2017 Jul 23. Epub 2017 Jul 23.
    Technological Innovation and Clinical Practice University Class (AINTEC), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
    Aims: To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus.

    Methods: AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. Read More

    Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta-analysis of cohort studies.
    Br J Clin Pharmacol 2017 Jul 21. Epub 2017 Jul 21.
    Department of Public Health, Izmir Katip Celebi University School of Medicine, Izmir, Turkey.
    We undertook an exclusive meta-analysis of cohort studies investigating the possible link between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autism spectrum disorders (ASD) in children to further investigate our previous suggestion of confounding by indication. The point estimates regarding the following cohorts were extracted and pooled: (1) pregnant women who discontinued SSRI until 3 months before pregnancy; (2) pregnant women who were exposed to SSRI during pregnancy; and (3) pregnant women with maternal psychiatric disorder but no exposure to SSRI during pregnancy. Although the pooled point estimate of the first cohort showed a trend for increase, it did not reach significance. Read More

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