11,356 results match your criteria British journal of clinical pharmacology[Journal]


Effects of Nigella sativa seeds (black cumin) on insulin secretion and lipid profile: a pilot study in healthy volunteers.

Br J Clin Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

CHU de Montpellier, Centre d'Investigation Clinique, Montpellier, France.

Nigella sativa seeds (NSS), also known as black cumin, have been claimed to have antidiabetic and lipid-lowering properties. Our pilot study investigated the effects of powdered NSS on insulin secretion and lipid profile in healthy male volunteers. We conducted a double blind randomized placebo-controlled 4-week trial in 30 subjects, receiving NSS powder (1 g/day) or placebo orally (15 subjects/group). Read More

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http://dx.doi.org/10.1111/bcp.13922DOI Listing

Can Cytidine deaminase be used as predictive biomarker for gemcitabine toxicity and response?

Br J Clin Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

SMARTc Unit, CRCM Inserm U1068 Aix Marseille Université, and La Timone University Hospital of Marseille, Marseille, France.

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http://dx.doi.org/10.1111/bcp.13921DOI Listing

Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first line immunochemotherapy.

Br J Clin Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

Pharma Development Oncology, F. Hoffmann-La Roche, Basel, Switzerland.

Aims: Obinutuzumab (G) is a humanized type II, Fc-glycoengineered anti-CD20 monoclonal antibody used in various indications, including patients with previously untreated follicular lymphoma (1L FL). We investigated sources of variability in G exposure and association of progression-free survival (PFS) with average concentration over induction (C ) in 1L FL patients treated with G plus chemotherapy (bendamustine, CHOP, or CVP) in the GALLIUM trial.

Methods: Individual exposures (C ) were obtained from a previously established population pharmacokinetic model updated with GALLIUM data. Read More

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http://dx.doi.org/10.1111/bcp.13920DOI Listing

Key enablers and barriers to implementing adaptive pathways in the European setting.

Br J Clin Pharmacol 2019 Mar 8. Epub 2019 Mar 8.

National Institute for Health and Care Excellence, Manchester, M1 4BT, UK.

In 2016, the European Medicines Agency (EMA) published the conclusions of its pilot on adaptive pathways, with products in early stages of development still building up to their marketing authorisation. Adaptive pathways rests on three principles: iterative development; gathering evidence through real-life use to supplement clinical trial data; and early engagement of patients, payers and health technology assessment bodies in discussions on a medicine's development. While the pilot has now finished, the practical system-wide implications of employing the adaptive pathways approach are not known and further consideration of these three principles is required. Read More

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http://dx.doi.org/10.1111/bcp.13916DOI Listing

Availability and readability of patient education materials for deprescribing: An environmental scan.

Br J Clin Pharmacol 2019 Mar 8. Epub 2019 Mar 8.

The University of Sydney, Sydney School of Public Health, ASK-GP Centre of Research Excellence, NSW, Australia.

Aims: To identify and evaluate content and readability of freely available online deprescribing patient education materials (PEMs).

Methods: Systematic review of PEMs using MEDLINE, Embase, CINAHL, PsycINFO and The Cochrane Library of Systematic Reviews from inception to September 25, 2017 to identify PEMs. Additionally, deprescribing researchers and health professionals were surveyed to identify additional materials. Read More

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http://dx.doi.org/10.1111/bcp.13912DOI Listing

Effects of proton pump inhibitors, esomeprazole and vonoprazan, on the disposition of proguanil, a CYP2C19 substrate, in healthy volunteers.

Br J Clin Pharmacol 2019 Mar 7. Epub 2019 Mar 7.

Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo, 202-8585, Japan.

Aims: Vonoprazan, a new class of potassium-competitive proton pump inhibitors (PPI) has been found to attenuate the antiplatelet function of clopidogrel in a recent clinical study, despite weak in vitro activity against CYP2C19. To elucidate the mechanism of this interaction, the present study investigated the effects of esomeprazole and vonoprazan on the pharmacokinetics of proguanil, a CYP2C19 substrate.

Methods: Seven healthy male volunteers (CYP2C19 extensive metabolizers) received a single oral administration of 100 mg proguanil/250 mg atovaquone (control phase), oral esomeprazole (20 mg) for 5 days followed by proguanil/atovaquone (esomeprazole phase), and oral vonoprazan (20 mg) for 5 days followed by proguanil/atovaquone (vonoprazan phase). Read More

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http://dx.doi.org/10.1111/bcp.13914DOI Listing
March 2019
1 Read

A multiple methods approach to determine adherence with prescribed mycophenolate in children with kidney transplant.

Br J Clin Pharmacol 2019 Mar 7. Epub 2019 Mar 7.

Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, Belfast, UK.

Aims: The aim of the present study was, to use a multiple methods approach, including, for the first time, dried blood spot (DBS) sampling with PopPK interpretation, to assess adherence to mycophenolate in children with kidney transplant. A second aim was to identify patient/parental factors that influenced adherence and to link adherence behaviour to clinical outcomes.

Methods: A convenience sample of 33 children with kidney transplant (≤18 years old) who had been prescribed mycophenolate for at least 3 months were recruited from participating outpatient clinics in the UK and Jordan. Read More

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http://dx.doi.org/10.1111/bcp.13911DOI Listing
March 2019
1 Read

Effect of CYP3A inhibitors on the pharmacokinetics of pevonedistat in patients with advanced solid tumours.

Br J Clin Pharmacol 2019 Mar 7. Epub 2019 Mar 7.

Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Aims: This phase I study evaluated the effects of the moderate cytochrome P450 (CYP) 3A inhibitor fluconazole and the strong CYP3A/P-glycoprotein (P-gp) inhibitor itraconazole on the pharmacokinetics of the investigational neural precursor cell expressed, developmentally downregulated 8 (NEDD8)-activating enzyme inhibitor pevonedistat in patients with advanced solid tumours.

Methods: Patients received single doses of intravenous pevonedistat 8 mg m , alone and with fluconazole (loading: 400 mg; maintenance: 200 mg once daily), or pevonedistat 8, 15, or 20 mg m , alone and with itraconazole 200 mg once daily. Serial blood samples for pevonedistat pharmacokinetics were obtained pre- and post-infusion on days 1 (alone) and 8 (with fluconazole/itraconazole). Read More

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http://doi.wiley.com/10.1111/bcp.13915
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http://dx.doi.org/10.1111/bcp.13915DOI Listing
March 2019
8 Reads

Acute interaction between oral glucose (75 g as Lucozade) and inorganic nitrate: decreased insulin clearance, but lack of blood pressure-lowering.

Br J Clin Pharmacol 2019 Mar 7. Epub 2019 Mar 7.

King's College London British Heart Foundation Centre, School of Cardiovascular Medicine and Sciences, Department of Clinical Pharmacology, London, UK.

Introduction: Dietary inorganic nitrate (NO ) lowers peripheral blood pressure (BP) in healthy volunteers, but lacks such effect in individuals with, or at risk of, type two diabetes mellitus. Whilst this is commonly assumed to be a consequence of chronic hyperglycaemia/hyperinsulinaemia, we hypothesised that acute physiological elevations in plasma [glucose]/[insulin] blunt the haemodynamic responses to NO ; a pertinent question for carbohydrate-rich Western diets.

Methods: We conducted an acute, randomised, placebo-controlled, double-blind, crossover study on the haemodynamic and metabolic effects of potassium nitrate (8 or 24 mmol KNO ) versus potassium chloride (KCl; placebo) administered 1 h prior to an oral glucose tolerance test in 33 healthy volunteers. Read More

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http://dx.doi.org/10.1111/bcp.13913DOI Listing

Associations of statin use with glycaemic traits and incident type 2 diabetes.

Br J Clin Pharmacol 2019 Mar 5. Epub 2019 Mar 5.

Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, the Netherlands.

Aims: There are several epidemiological studies on the association between statins and incident diabetes, but most of them lack details. In this study, we aimed to investigate the association of statin use with glycaemic traits and incident type 2 diabetes.

Methods: Using the prospective population-based Rotterdam Study, we included 9,535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Read More

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http://dx.doi.org/10.1111/bcp.13898DOI Listing
March 2019
4 Reads

A Six Sigma framework to successfully manage medication adherence.

Authors:
Bernard Vrijens

Br J Clin Pharmacol 2019 Mar 4. Epub 2019 Mar 4.

Research and Development, AARDEX Group, Liège, Belgium.

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http://dx.doi.org/10.1111/bcp.13905DOI Listing

Maturational changes in vancomycin protein binding affect vancomycin dosing in neonates.

Br J Clin Pharmacol 2019 Mar 4. Epub 2019 Mar 4.

Department of Development and Regeneration, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1111/bcp.13899DOI Listing
March 2019
3.878 Impact Factor

Reply to 'Comment on 'Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double-blind, randomised controlled VaSera trial' by Faconti et al.'

Br J Clin Pharmacol 2019 Mar 4. Epub 2019 Mar 4.

King's College London British Heart Foundation Centre, Department of Clinical Pharmacology, School of Cardiovascular Medicine and Sciences, London, UK.

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http://dx.doi.org/10.1111/bcp.13890DOI Listing

Activity and mRNA expression levels of selected cytochromes P450 in various sections of the human small intestine.

Br J Clin Pharmacol 2019 Feb 28. Epub 2019 Feb 28.

Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada.

Aims: To characterize mRNA expression levels (17 cytochromes P450) and activity (9 isoforms) of major cytochromes P450 expressed throughout the human small intestine.

Methods: Tissue samples were obtained from 9 deceased subjects and intestinal sections (n=10) were isolated for each subject. Relative mRNA expression levels were determined using quantitative real-time PCR. Read More

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http://dx.doi.org/10.1111/bcp.13908DOI Listing
February 2019

Cetuximab Pharmacokinetic/Pharmacodynamics relationships in advanced head and neck carcinoma patients.

Br J Clin Pharmacol 2019 Feb 27. Epub 2019 Feb 27.

Laboratory of Pharmacology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.

Aims: Cetuximab associated with cisplatin and 5-fluorouracil is used to treat patients with inoperable or metastatic head and neck squamous cell carcinomas up until disease progression or unacceptable toxicities. To date, no biomarkers of efficacy are available to select patients who will benefit from treatment.

Methods: An ancillary pharmacokinetics (PK) exploration was performed in the context of a prospective study investigating circulating-tumor cells vs. Read More

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http://dx.doi.org/10.1111/bcp.13907DOI Listing
February 2019
4 Reads
3.878 Impact Factor

Interaction of OTC drug noscapine and acenocoumarol and phenprocoumon.

Br J Clin Pharmacol 2019 Feb 26. Epub 2019 Feb 26.

Reporting Department, Netherlands Pharmacovigilance Centre Lareb, 's-Hertogenbosch, The Netherlands.

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http://dx.doi.org/10.1111/bcp.13887DOI Listing
February 2019

Methadone dosing strategies in preterm neonates can be simplified.

Br J Clin Pharmacol 2019 Feb 25. Epub 2019 Feb 25.

Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland.

Aims: A dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics (PK) of methadone is available in preterm neonates. Therefore we investigated developmental PK of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population. Read More

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http://doi.wiley.com/10.1111/bcp.13906
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http://dx.doi.org/10.1111/bcp.13906DOI Listing
February 2019
3 Reads
3.878 Impact Factor

Predicting the dose of vancomycin in ICU patients receiving different types of RRT therapy: a model-based meta-analytic approach.

Br J Clin Pharmacol 2019 Feb 15. Epub 2019 Feb 15.

Unité de Recherche Clinique, Innovation, Pharmacologie, Hôpital Nord, CHU de Saint-Etienne, F-42055, Saint-Etienne, France.

Aim: Previous pharmacokinetic (PK) studies have proposed various dosing regimens for vancomycin in intensive care unit (ICU) patients undergoing renal replacement therapy (RRT), but all are restricted to specific RRT modalities. To be useful in practice, a population PK model would need to predict vancomycin clearance during any RRT modality. Development of such a model is feasible using meta-analysis of published summarised estimates of vancomycin PK parameters. Read More

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http://dx.doi.org/10.1111/bcp.13904DOI Listing
February 2019

Handling interoccasion variability in model-based dose individualization using therapeutic drug monitoring data.

Br J Clin Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Aims: This study aims to assess approaches to handle interoccasion variability (IOV) in a model-based therapeutic drug monitoring (TDM) context, using a population pharmacokinetic model of coagulation factor VIII as example.

Methods: We assessed five model-based TDM approaches: empirical Bayes estimates (EBEs) from a model including IOV, with individualized doses calculated based on individual parameters either (i) including or (ii) excluding variability related to IOV; and EBEs from a model excluding IOV by (iii) setting IOV to zero, (iv) summing variances of interindividual variability (IIV) and IOV into a single IIV term, or (v) re-estimating the model without IOV. The impact of varying IOV magnitudes (0-50%) and number of occasions/observations was explored. Read More

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http://dx.doi.org/10.1111/bcp.13901DOI Listing
February 2019
1 Read

Effects of Dapagliflozin vs. Vildagliptin on Cardiometabolic Parameters in Diabetic Patients with Coronary Artery Disease: A Randomised Study.

Br J Clin Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Aims: SGLT2 inhibitors have been shown to reduce cardiovascular (CV) events and heart failure (HF) in type 2 diabetic (T2D) patients with high CV risk. DPP-4 inhibitors showed neutral effects and may increase risk of HF. We aimed to compare cardiometabolic effects of dapagliflozin and vildagliptin in T2D patients with coronary artery disease (CAD). Read More

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http://doi.wiley.com/10.1111/bcp.13903
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http://dx.doi.org/10.1111/bcp.13903DOI Listing
February 2019
7 Reads

A semiphysiological population pharmacokinetic model of agomelatine and its metabolites in Chinese healthy volunteers.

Br J Clin Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Research Institute of Drug Metabolism and Pharmacokinetics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.

Aims: Agomelatine is an antidepressant for major depressive disorders. It undergoes extensive first-pass hepatic metabolism, and displays irregular absorption profiles and large interindividual variability (IIV) and interoccasion variability (IOV) of pharmacokinetics. The objective of this study was to characterize the complex pharmacokinetics of agomelatine and its metabolites in healthy subjects. Read More

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http://doi.wiley.com/10.1111/bcp.13902
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http://dx.doi.org/10.1111/bcp.13902DOI Listing
February 2019
2 Reads

Bridging adults and paediatrics with secondary hyperparathyroidism receiving haemodialysis: a pharmacokinetic-pharmacodynamic analysis of cinacalcet.

Br J Clin Pharmacol 2019 Feb 12. Epub 2019 Feb 12.

Amgen, Inc., Thousand Oaks, CA, USA.

Aims: To develop a pharmacokinetic (PK) and PK-pharmacodynamic (PK/PD) model of cinacalcet, in adults and paediatrics with secondary hyperparathyroidism (SHPT) on dialysis. To test covariates of interest, and to perform simulations to inform dosing in paediatrics with SHPT.

Methods: Cinacalcet PK, intact parathyroid hormone (iPTH) and corrected calcium (cCa) time courses following multiple daily oral doses (1-300 mg) were modelled using a nonlinear mixed effects modelling approach using data from 8 clinical studies. Read More

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http://dx.doi.org/10.1111/bcp.13900DOI Listing
February 2019
1 Read

Fluid volume kinetics of 20% albumin.

Br J Clin Pharmacol 2019 Feb 12. Epub 2019 Feb 12.

Perioperative Medicine and Intensive Care, Karolinska University Hospital, Solna, Sweden.

Aims: A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery.

Methods: An intravenous infusion of 3 mL/kg 20% albumin over 30 min was given to 15 volunteers and to 15 patients on the first day after major open abdominal surgery. Read More

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http://dx.doi.org/10.1111/bcp.13897DOI Listing
February 2019
1 Read

Pharmacokinetics and Pharmacodynamics of Voxelotor (GBT440) in Healthy Adults and Patients With Sickle Cell Disease.

Br J Clin Pharmacol 2019 Feb 11. Epub 2019 Feb 11.

Global Blood Therapeutics, South San Francisco, CA, USA.

Aims: Voxelotor (previously GBT440) is a hemoglobin (Hb) modulator that increases Hb-oxygen affinity, thereby reducing Hb polymerization and sickling of red blood cells (RBCs), being developed as a once-daily oral drug to treat sickle cell disease (SCD). This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of voxelotor in healthy volunteers and SCD patients.

Methods: A total of 40 healthy volunteers (100, 400, 1000, 2000, or 2800 mg) and 8 SCD patients (1000 mg) were randomly assigned to a single dose of voxelotor once daily (n = 6 per group) or placebo (n = 2 per group). Read More

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http://dx.doi.org/10.1111/bcp.13896DOI Listing
February 2019
3 Reads

Five-year trends in Acetaminophen use exceeding the recommended daily maximum dose.

Br J Clin Pharmacol 2019 Feb 10. Epub 2019 Feb 10.

Pinney Associates, Pittsburgh, PA.

Temporal patterns of acetaminophen use exceeding the recommended daily maximum 4-gram dose over a 5-year period (4/1/2011-3/31/2016) were evaluated in an online 1-week diary study of 14,434 adult acetaminophen users who also reported acetaminophen use in the previous month. Specific medications taken were identified by list-based prompting; respondents were not required to know their medications contained acetaminophen. Details of use were recorded daily; total daily dosage was determined programmatically. Read More

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http://dx.doi.org/10.1111/bcp.13894DOI Listing
February 2019

Cabozantinib-related cardiotoxicity: a prospective analysis in a "real world" cohort of metastatic renal cell carcinoma patients.

Br J Clin Pharmacol 2019 Feb 10. Epub 2019 Feb 10.

Department of Medical Oncology, Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, Italy.

Aims: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients.

Methods: We performed a multicenter prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Read More

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http://dx.doi.org/10.1111/bcp.13895DOI Listing
February 2019
2 Reads
3.878 Impact Factor

Effects of prednisone on docetaxel pharmacokinetics in men with metastatic prostate cancer: A randomized drug-drug interaction study.

Br J Clin Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Aim: Docetaxel has been approved for the treatment of metastatic prostate cancer in combination with prednisone. Since prednisone is known to induce the cytochrome P450 iso-enzyme CYP3A4, which is the main metabolizing enzyme of docetaxel in the liver, a potential drug-drug interaction (DDI) may occur. In this prospective randomized pharmacokinetic cross-over study we investigated docetaxel exposure with concomitant prednisone, compared to docetaxel monotherapy in men with metastatic prostate cancer. Read More

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http://dx.doi.org/10.1111/bcp.13889DOI Listing
February 2019
1 Read

Patterns of gabapentin and pregabalin use and misuse: results of a population-based cohort study in France.

Br J Clin Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Unité Mixte de Recherche 1027 Inserm-Université, Pharmacoépidémiologie, Université de Toulouse, France.

Aims: The aim of this study was to assess the use and factors associated with misuse of gabapentin and pregabalin in the general French population, through a cohort study in the EGB (General Sample of Beneficiaries), a national representative sample of the French general population.

Methods: New users of gabapentin and pregabalin were identified from June 2006 to December 2014, and new users of duloxetine served as control group. Misuse was defined as a use of higher daily doses than recommended. Read More

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http://dx.doi.org/10.1111/bcp.13892DOI Listing
February 2019
1 Read

Case report by Toce and co-authors: Have all the reasons for poor morphine glucuronidation been addressed?

Br J Clin Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1111/bcp.13868DOI Listing
February 2019

Population/regional differences in efficacy of three drug categories (antidiabetic, respiratory, and psychotropic agents) among East Asians: A retrospective study based on multi-regional clinical trials.

Br J Clin Pharmacol 2019 Feb 8. Epub 2019 Feb 8.

Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan.

Aims: This study aimed to identify population/regional differences in drug efficacy and the influencing factors among East Asians to be considered when planning multi-regional clinical trials (MRCTs) to facilitate rapid drug approval in Asians.

Methods: A retrospective analysis of efficacy (intergroup difference in endpoint between control and study drug treatment) among East Asian populations for three drug categories, antidiabetic, respiratory, and psychotropic agents, was conducted in collaboration with pharmaceutical companies using their MRCT data. Common endpoints by drug category were selected; background factors that commonly affected the endpoints among regions were analysed first; then, the population/regional differences were evaluated by the interaction term "region-by-treatment" using an analysis of covariance model after adjusting for background factors. Read More

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http://dx.doi.org/10.1111/bcp.13893DOI Listing
February 2019
2 Reads

Population pharmacokinetic-pharmacodynamic modelling of the relationship between testosterone and PSA in patients with prostate cancer during treatment with leuprorelin.

Br J Clin Pharmacol 2019 Feb 7. Epub 2019 Feb 7.

Takeda Development Centre Europe Ltd, London, United Kingdom.

Aims: This investigation aimed to quantitatively characterize the relationship between the gonadotropin-releasing hormone (GnRH) agonist leuprorelin, testosterone (T) and Prostate specific antigen (PSA) concentrations over time, to aid identification of a target T concentration which optimises the balance of the benefits of T suppression whilst reducing the risk of side effects related to futile over-suppression.

Methods: Data from a single dose study to investigate the effect of leuprorelin in a 6-month depot formulation on T and PSA in prostate cancer patients were analysed using a population pharmacokinetic-pharmacodynamic (PKPD) modelling approach. The developed model was qualified using external data from three studies, in which the effect of different formulations of leuprorelin on T and PSA was evaluated in prostate cancer patients. Read More

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http://dx.doi.org/10.1111/bcp.13891DOI Listing
February 2019
1 Read

The skeletal impact of cancer therapies.

Br J Clin Pharmacol 2019 Feb 5. Epub 2019 Feb 5.

Division of Endocrinology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905, USA.

Both cancer and therapies used in the treatment of cancer can have significant deleterious effects on the skeleton, increasing the risks for both bone loss and fracture development. While advancements in cancer therapies have resulted in enhanced cancer survivorship for patients with many types of malignancies, it is increasingly recognized that efforts to reduce bone loss and limit fractures must be considered for nearly all patients undergoing cancer therapy in order to diminish the anticipated future skeletal consequences. To date, most studies examining the impact of cancer therapies on skeletal outcomes have focused on endocrine-associated cancers of the breast and prostate, with more recent advances in our understanding of bone loss and fracture risk in other malignancies. Read More

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http://dx.doi.org/10.1111/bcp.13866DOI Listing
February 2019

Efficacy and safety of sapropterin dihydrochloride in patients with phenylketonuria: A meta-analysis of randomized controlled trials.

Br J Clin Pharmacol 2019 Feb 5. Epub 2019 Feb 5.

Department of Pharmacy, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, P.R. China.

Aims: The aim of the present meta-analysis was to evaluate the efficacy and safety of sapropterin dihydrochloride in phenylketonuria (PKU) patients.

Methods: The following databases were searched for randomized controlled trials (RCT) regarding PKU patients treated with sapropterin dihydrochloride: Pubmed, Embase, Cochrane Library and clinicaltrials. Two authors independently selected studies, assessed the risk of bias and extracted data. Read More

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http://dx.doi.org/10.1111/bcp.13886DOI Listing
February 2019
5 Reads

Central nervous system effects of the histamine-3 receptor antagonist CEP-26401, in comparison with modafinil and donepezil, after a single dose in a cross-over study in healthy volunteers.

Br J Clin Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Research and Development Teva Pharmaceuticals, Netanya, Israel.

Aims: In previous studies, the histamine-3 receptor antagonist CEP-26401 had a subtle effect on spatial working memory, with the best effect seen at the lowest dose tested (20 μg), and a dose-dependent disruption of sleep. In the current study, 3 low-dose levels of CEP-26401 were compared with modafinil and donepezil.

Methods: In this double-blind, placebo- and positive-controlled, randomized, partial 6-way cross-over study, 40 healthy subjects received single doses of placebo, CEP-26401 (5, 25 or 125 μg) or modafinil 200 mg or donepezil 10 mg. Read More

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http://dx.doi.org/10.1111/bcp.13885DOI Listing
February 2019
1 Read

Pharmacokinetics of ticarcillin-clavulanate in premature infants.

Br J Clin Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Duke University Medical Center, Durham, NC, USA.

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. Read More

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http://dx.doi.org/10.1111/bcp.13882DOI Listing
February 2019

Commentary on the EMA Reflection Paper on the use of extrapolation in the development of medicines for paediatrics.

Br J Clin Pharmacol 2019 Feb 1. Epub 2019 Feb 1.

Licensing Division, Medicines and Healthcare products Regulatory Agency, London, UK.

Adopted guidelines reflect a harmonised European approach to a specific scientific issue and should reflect the most recent scientific knowledge. However, whilst EU regulations are mandatory for all member states and EU directives must be followed by national laws in line with the directive, EMA guidelines do not have legal force and alternative approaches may be taken, but these obviously require more justification. This new series of the BJCP, developed in collaboration with the EMA, aims to address this issue by providing an annotated version of some relevant EMA guidelines and regulatory documents by experts. Read More

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http://dx.doi.org/10.1111/bcp.13883DOI Listing
February 2019
1 Read

Evaluating metronidazole as a novel, safe CYP2A6 phenotyping probe in healthy adults.

Br J Clin Pharmacol 2019 Feb 1. Epub 2019 Feb 1.

Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Children's Mercy Kansas City, MO, USA.

Aims: CYP2A6 is a genetically polymorphic enzyme resulting in differential substrate metabolism and health behaviours. Current phenotyping probes for CYP2A6 exhibit limitations related to procurement (deuterated cotinine), toxicity (coumarin), specificity (caffeine) and age-appropriate administration (nicotine, NIC). In vitro, CYP2A6 selectively forms 2-hydroxymetronidazole (2HM) from metronidazole (MTZ). Read More

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http://dx.doi.org/10.1111/bcp.13884DOI Listing
February 2019
2 Reads

Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours.

Br J Clin Pharmacol 2018 Dec 27. Epub 2018 Dec 27.

Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.

Aims: Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this interindividual variability. Read More

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http://dx.doi.org/10.1111/bcp.13849DOI Listing
December 2018

Pharmacokinetic herb-drug interaction between ginger and crizotinib.

Br J Clin Pharmacol 2019 Jan 30. Epub 2019 Jan 30.

Institute for Advanced Biosciences, UGA/INSERM U1209/CNRS 5309, Université Grenoble Alpes, France.

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http://dx.doi.org/10.1111/bcp.13862DOI Listing
January 2019

Relationship between allograft cyclosporin concentrations and P-glycoprotein expression in the 1st month following renal transplantation.

Br J Clin Pharmacol 2019 Jan 28. Epub 2019 Jan 28.

Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, SA, 5000, Australia.

The immunosuppressant cyclosporin is a P-glycoprotein (P-gp) substrate whose impaired function has been associated with an increased risk of cyclosporin-induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P-gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression. Read More

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http://dx.doi.org/10.1111/bcp.13880DOI Listing
January 2019

Pharmacometrics and systems pharmacology for metabolic bone diseases.

Br J Clin Pharmacol 2019 Jan 28. Epub 2019 Jan 28.

Departments of Pathology & Cell Biology and Medicine, Columbia University Medical Center, New York, NY, USA.

Mathematical modelling and simulation (M&S) of drug concentrations, pharmacologic effects and the (patho)physiologic systems within which they interact can be powerful tools for the preclinical, translational and clinical development of drugs. Indeed, the Prescription Drug User Fee Act (PDUFA VI), incorporated as part of the FDA Reauthorization Act of 2017 (FDARA), highlights the goal of advancing model-informed drug development (MIDD). MIDD can benefit development across many drug classes, including for metabolic bone diseases such as osteoporosis, cancer-related and numerous rare metabolic bone diseases; conditions characterized by significant morbidity and mortality. Read More

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http://dx.doi.org/10.1111/bcp.13881DOI Listing
January 2019
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Response to 'Sex-by-formulation interaction in bioequivalence studies: the importance of formulations and experimental conditions' by Ibarra et al.

Br J Clin Pharmacol 2019 Jan 28. Epub 2019 Jan 28.

Service on Pharmacokinetics and Generics, Division of Pharmacology and Clinical Evaluation, Department of Human Use Medicines, Spanish Agency for Medicines and Health Care Products, Madrid, Spain.

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http://dx.doi.org/10.1111/bcp.13860DOI Listing
January 2019
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Clinical implications of the association between fluoroquinolones and tendon rupture: the magnitude of the effect with and without corticosteroids.

Br J Clin Pharmacol 2019 Jan 25. Epub 2019 Jan 25.

Boston Collaborative Drug Surveillance Program, 11 Muzzey Street, Lexington, MA, USA.

Aims: To estimate the relative, absolute, and attributable risk of non-traumatic tendon rupture, at various sites, associated with use of fluoroquinolones, with and without concomitant corticosteroids.

Methods: We conducted cohort and nested case-control studies among fluoroquinolone users in the United Kingdom Clinical Practice Research Datalink Gold. We estimated the excess risk (cohort analysis) and odds ratios (ORs) (case control) of tendon rupture by fluoroquinolone (current, recent and past use verses unexposed) and corticosteroid (current versus unexposed) use. Read More

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http://dx.doi.org/10.1111/bcp.13879DOI Listing
January 2019
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Under-representation of elderly in clinical trials: An analysis of the initial approval documents in the Food and Drug Administration database.

Br J Clin Pharmacol 2019 Jan 25. Epub 2019 Jan 25.

Centre for Human Drug Research, Leiden, the Netherlands.

Aims: To evaluate the availability of pharmacokinetic, safety and efficacy analyses specifically targeted at elderly, prior to the authorization of drugs.

Methods: A cross-sectional, structured review of publicly available initial approval documents of Food and Drug Administration-approved drugs was performed. The 10 most frequently on-label prescribed drug classes, drugs with known pharmacokinetic differences in the elderly or drugs that are relatively contraindicated in elderly (e. Read More

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http://dx.doi.org/10.1111/bcp.13876DOI Listing
January 2019

Treatment of exudative age-related macular degeneration with aflibercept combined with pranoprofen eye drops or nutraceutical support with omega-3: A randomized trial.

Br J Clin Pharmacol 2019 Jan 24. Epub 2019 Jan 24.

Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, Italy.

Aims: The aim of this study was to determine whether a combination of intravitreal aflibercept (IVA) and pranoprofen eyedrops or nutraceutical support provides additional benefit over IVA monotherapy for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration.

Methods: This was a prospective, randomized, pilot study in 60 patients with treatment-naïve CNV. Patients were randomized 1:1:1 into three groups: aflibercept monotherapy (AM), aflibercept plus pranoprofen (AP) or aflibercept plus nutraceutical (AN) tablets containing multivitamin antioxidant and mineral supplementation plus omega-3. Read More

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http://dx.doi.org/10.1111/bcp.13871DOI Listing
January 2019

Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease.

Br J Clin Pharmacol 2019 Jan 24. Epub 2019 Jan 24.

Eli Lilly and Company, Indianapolis, Indiana, USA.

Aims: Erythropoiesis-stimulating agents used to treat anaemia in patients with chronic kidney disease (CKD) have been associated with cardiovascular adverse events. Hepcidin production, controlled by bone morphogenic protein 6 (BMP6), regulates iron homeostasis via interactions with the iron transporter, ferroportin. High hepcidin levels are thought to contribute to increased iron sequestration and subsequent anaemia in CKD patients. Read More

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http://dx.doi.org/10.1111/bcp.13877DOI Listing
January 2019
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Effect of continuous venovenous haemodialysis on outcome and pharmacokinetics of arsenic species in a patient with acute promyelocytic leukaemia and acute kidney injury.

Br J Clin Pharmacol 2019 Jan 24. Epub 2019 Jan 24.

Department of Pharmacy, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.

This study presents outcome and pharmacokinetics of arsenic trioxide (ATO) metabolites in patients on continuous venovenous haemodialysis (CVVHD). Of 3 acute promyelocytic leukaemia patients receiving CVVHD in management of acute kidney injury, only 1 patient was included. The patient presented disseminated intravascular coagulation and acute kidney injury before induction therapy was conducted. Read More

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http://doi.wiley.com/10.1111/bcp.13875
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http://dx.doi.org/10.1111/bcp.13875DOI Listing
January 2019
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Ensuring continuity of patient care across the healthcare interface: Telephone follow-up post-hospitalization.

Br J Clin Pharmacol 2019 Mar 24;85(3):616-625. Epub 2019 Jan 24.

Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK.

Aims: To implement pharmacist-led, postdischarge telephone follow-up (TFU) intervention and to evaluate its impact on rehospitalization parameters in polypharmacy patients, via comparison with a well-matched control group.

Method: Pragmatic, prospective, quasi-experimental study. Intervention patients were matched by propensity score techniques with a control group. Read More

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http://dx.doi.org/10.1111/bcp.13839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379220PMC
March 2019
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Population pharmacokinetics of lenalidomide in patients with B-cell malignancies.

Br J Clin Pharmacol 2019 Jan 22. Epub 2019 Jan 22.

Australian Centre for Pharmacometrics, School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Australia.

Aims: Lenalidomide is an immunomodulatory imide drug used broadly in the treatment of multiple myeloma and lymphoma. It continues to be evaluated in chronic lymphocytic leukaemia (CLL) at lower doses due to dose-related toxicities including tumour flare and tumour lysis syndrome. This study aimed to develop a population pharmacokinetic model for lenalidomide in multiple cancers, including CLL, to identify any disease-related differences in disposition. Read More

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http://dx.doi.org/10.1111/bcp.13873DOI Listing
January 2019
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