British Journal of Clinical Pharmacology Impact Factor & Information

Publisher: British Pharmacological Society, Wiley

Journal description

The Journal of The British Pharmacological Society. Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology contains papers and reports on all aspects of drug action in humans: invited review articles, original papers, short communications and correspondence. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. Proceedings of the meetings of the Clinical Section of the British Pharmacological Society are published in abstract form and supplements containing information on new methods, new drugs and new approaches to treatment are supplied free of charge.

Current impact factor: 3.88

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.878
2013 Impact Factor 3.688
2012 Impact Factor 3.578
2011 Impact Factor 2.958
2010 Impact Factor 3.063
2009 Impact Factor 3.246
2008 Impact Factor 3.128
2007 Impact Factor 2.681
2006 Impact Factor 2.718
2005 Impact Factor 2.777
2004 Impact Factor 2.546
2003 Impact Factor 2.531
2002 Impact Factor 2.274
2001 Impact Factor 2.213
2000 Impact Factor 2.151
1999 Impact Factor 2.545
1998 Impact Factor 1.846
1997 Impact Factor 1.809
1996 Impact Factor 2.214
1995 Impact Factor 2.048
1994 Impact Factor 1.922
1993 Impact Factor 1.891
1992 Impact Factor 1.733

Impact factor over time

Impact factor

Additional details

5-year impact 3.83
Cited half-life 8.90
Immediacy index 0.89
Eigenfactor 0.02
Article influence 1.15
Website British Journal of Clinical Pharmacology website
Other titles British journal of clinical pharmacology (Online), BJCP
ISSN 1365-2125
OCLC 45425630
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Some journals have separate policies, please check with each journal directly
    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
    • Author's pre-print may not be updated with Publisher's Version/PDF
    • Author's pre-print must acknowledge acceptance for publication
    • Non-Commercial
    • Publisher's version/PDF cannot be used
    • Publisher source must be acknowledged with citation
    • Must link to publisher version with set statement (see policy)
    • If OnlineOpen is available, BBSRC, EPSRC, MRC, NERC and STFC authors, may self-archive after 12 months
    • If OnlineOpen is available, AHRC and ESRC authors, may self-archive after 24 months
    • Publisher last contacted on 07/08/2014
    • This policy is an exception to the default policies of 'Wiley'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer health care providers important information for the individualized treatment and follow-up of affected patients. Here a novel methodology is presented to make such estimates using a standard serum paracetamol measurement and a computational framework. Methods: The core component of the computational framework was a physiologically-based pharmacokinetic (PBPK) model developed and evaluated using an extensive set of human PK data. Bayesian inference was used for parameter and dose estimation, allowing the incorporation of inter-study variability, and facilitating the calculation of uncertainty in model outputs. Results: Simulations of paracetamol time-course concentrations in the blood were in close agreement to experimental data under a wide range of dosing conditions. Also, predictions of administered dose showed good agreement to a large collection of clinical and emergency-setting PK data over a broad dose range. In addition to dose estimation, the platform was applied for the determination of optimal blood sampling times for dose reconstruction and quantitation of the potential role of paracetamol conjugate measurement on dose estimation. Conclusions: Current therapies for paracetamol overdose rely on a generic methodology involving the use of a clinical nomogram. By using the computational framework developed in this study, serum sample data, and the individual patient's anthropometric and physiological information, personalized serum and liver pharmacokinetic profiles and dose estimate could be generated to help inform an individualized overdose treatment and follow-up plan. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 10/2015; DOI:10.1111/bcp.12796
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: The primary objective of this study was to evaluate pharmacokinetic and pharmacodynamic interactions between clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes. Methods: In a randomized, 3-way crossover study, 27 healthy subjects were administered clopidogrel (300 mg), cilostazol (100 mg), or clopidogrel + cilostazol orally. Plasma concentrations of clopidogrel, cilostazol and their active metabolites (clopidogrel thiol metabolite, 3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol), and ADP-induced platelet aggregation were measured for pharmacokinetic and pharmacodynamic assessment. Results: The area under the plasma concentration-time curve (AUC) of clopidogrel active thiol metabolite was highest in CYP2C19 extensive metabolizer (EM) and lowest in poor metabolizers (PM). Cilostazol decreased thiol metabolite AUC 29% in CYP3A5*1/*3 (Geometric mean ratio (GMR), 0.71; 90% CI, 0.58-0.86; p = 0.020) but not in CYP3A5*3/*3 (GMR, 0.93; 90% CI, 0.80-1.10; p = 0.446). Known CYP2C19 or CYP3A5 genotype effects on cilostazol and its metabolites exposure were observed, but there was no significant difference in the AUC of cilostazol and 3,4-dehydro-cilostazol between cilostazol and clopidogrel + cilostazol. The inhibition of platelet aggregation from 4 hrs to 24 hrs (IPA4-24 ) following administration of clopidogrel alone was highest in CYP2C19 EM genotype, and lowest in CYP2C19 PM genotype (59.05 ± 18.95 vs. 36.74 ± 13.26, P = 0.023). However, IPA of CYP2C19 PM following co-administration of clopidogrel and cilostazol was comparable to that of CYP2C19 EM and IM only in CYP3A5*3/*3. Conclusions: Additive antiplatelet effect of cilostazol to clopidogrel is maximized in subjects with both CYP2C19PM and CYP3A5*3/*3 because of lack of change of clopidogrel thiol metabolite exposure in CYP3A5*3/*3 as well as the highest cilostazol IPA in CYP2C19 PM or CYP3A5*3/*3. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 10/2015; DOI:10.1111/bcp.12794
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sometimes mistakenly characterized as a "universal antidote," activated charcoal (AC) is the most frequently employed method of gastrointestinal decontamination in the developed world. Typically administered as a single dose (SDAC), its tremendous surface area permits the binding of many drugs and toxins in the gastrointestinal lumen, reducing their systemic absorption. Like other decontamination procedures the utility of SDAC attenuates with time, and while generally safe it is not free of risk. A large body of evidence demonstrates that SDAC can reduce the absorption of drugs and xenobiotics, but most such studies involve volunteers and have little generalizability to clinical practice. Few rigorous clinical trials of SDAC have been conducted, and none validate or refute its utility in those patients who are intuitively most likely to benefit. Over the past decade, a growing body of observational data demonstrates that SDAC can elicit substantial reductions in drug absorption in acutely poisoned patients. The challenge for clinicians rests in differentiating those patients most likely to benefit from SDAC from those in whom meaningful improvement is doubtful. This is often a difficult determination not well suited to an algorithmic approach. This narrative review summarizes the data supporting the benefits and harms of SDAC, and offers pragmatic suggestions for clinical practice. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12793
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Pridopidine, a new oral drug for treatment of patients with motor symptoms associated with Huntington's Disease (HD) is currently under development. In steady state conditions, pridopidine elimination is mediated primarily through renal excretion. This study evaluated single-dose and steady-state pharmacokinetics (PK) of a daily dose of pridopidine in subjects with mild and moderate renal impairment and matched healthy subjects. Methods: Subjects with mild renal impairment (n = 12), moderate impairment (n = 12), or their matched healthy controls (n = 25) participated in this study. Subjects received a single dose of pridopidine (45 mg) on Day 1 and a multiple dose cycle of 45 mg once daily on Days 5-18. Blood and urine samples were collected on Days 1 and 18 for PK analysis. Results: Mild renal impairment did not affect the PK of pridopidine whilst an increase in exposure was seen in subjects with moderate renal impairment. Subjects with moderate impairment showed reduced plasma clearance (by 44%) and had 68% higher AUC (90% CI 1.22 - 2.30) and 26% higher Cmax (90% CI 1.02 - 1.56) values than those with normal renal function at steady-state. Pridopidine was safe and well tolerated in healthy subjects and in subjects with mild and moderate renal impairment. Conclusions: Mild renal impairment has no impact on exposure to pridopidine while moderately impaired renal function resulted in higher pridopidine concentrations. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12792
  • British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12791
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: 5-FU is the backbone of most regimens in digestive oncology. Administration of standard 5-FU leads to 15-30% of severe side-effects, and lethal toxicities are regularly reported with fluoropyrimidine drugs. DPD deficiency is a pharmacogenetic syndrome responsible for most cases of life-threatening toxicities upon 5-FU intake, and pre-treatment checking for DPD status should help to reduce both incidence and severity of side-effects through adaptive dosing strategies. Methods: We have used a simple method for rapidly establishing the DPD phenotype of patients with cancer and used it prospectively in 59 routine patients treated with 5-FU-based therapy for digestive cancers. No patient with total DPD deficiency was found but 23 % of patients exhibited poor metabolizer phenotype, and one patient was phenotyped as profoundly deficient. Consequently, 5-FU doses in poor metabolizer patients were cut by an average 35% (2390 ± 1225 mg VS. 3653 ± 1371 mg, p < 0.003, t test). Results: Despite this marked reduction in 5-FU dosing, similar efficacy was achieved in the two subsets (clinical benefit: 40 VS. 43 %, stable disease: 40 VS. 37%, progressive disease: 20 % in both subsets, p = 0.893, Pearson's Chi-Square). No difference in toxicities was observed (p = 0.104, Fischer Exact Test). Overall, only 3% of early severe toxicities were recorded, a value markedly lower than the ones usually reported with 5-FU. Conclusions: This feasibility study shows how simplified DPD-based adaptive dosing of 5-FU can reduce sharply the incidence of treatment-related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12790
  • British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12695
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma is a brain neoplasm with limited 5-year survival rates. Developments of new treatment regimens that improve patient survival in patients with glioblastoma are needed. It is likely that a number of existing drugs used in other conditions have potential anti-cancer effects that offer significant survival benefit to glioblastoma patients. Identification of such drugs could provide a novel treatment paradigm.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12785
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite being a major clinical and public health problem across the developing world, responsible for at least 5 million deaths over the last three decades, the clinical care of patients with organophosphorus insecticide poisoning has little improved over the last six decades. We are still using the same two antidotes - atropine and oximes - that first came into clinical use in the late 1950s. Clinical research in South Asia has shown how improved regimens of atropine can prevent deaths. However, we are still unsure about which patients are most likely to benefit from the use of oximes. Supplemental antidotes, such as magnesium, clonidine, and sodium bicarbonate, have all been proposed and studied in small trials without production of definitive answers. Novel antidotes such as nicotinic antagonists, beta-adrenergic agonists, and lipid emulsions are being studied in large animal models and in pilot clinical trials. Hopefully, one or more of these affordable and already licensed antidotes will find their place in routine clinical care. However, the large number of chemically diverse OP insecticides, the varied poisoning they produce, and their varied response to treatment, may ultimately make it very difficult to definitively determine whether these antidotes are truly effective. In addition, the toxicity of the varied solvents and surfactants formulated with the OP active ingredients complicates both treatment and studies. It is possible that the only effective way to reduce deaths from OP insecticide poisoning will be a steady reduction in their agricultural use worldwide. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12784
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting once-daily inhaled bronchodilator approved for treatment of COPD. It was the aim to describe olodaterol plasma and urine pharmacokinetics after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer about its pulmonary fate. Methods: Plasma and urine data after intravenous administration (0.5 - 25 µg) and oral inhalation (2.5 - 70 µg via the Respimat® inhaler) were available from a total number of 148 healthy volunteers (single and multiple dosing). A stepwise model building approach was applied using a population pharmacokinetic approach. Systemic disposition parameters were fixed to estimates obtained from intravenous data when modelling data after inhalation. Results: A pharmacokinetic model including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four compartment body model (systemic disposition model) was found to describe the data the best. The dose reaching the lung (pulmonary bioavailable fraction) was estimated to be 49.4% (46.1 - 52.7%, 95% confidence interval) of the dose released from the device. A large fraction of the pulmonary bioavailable fraction (70.1% (66.9 - 73.3%)) was absorbed with a half-life of 21.8 h (19.7 - 24.3 h). Conclusions: Plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers were adequately described. The key finding was that a high fraction of the pulmonary bioavailable fraction had an extended pulmonary residence time. This finding was not expected based on physico-chemical properties of olodaterol. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12780
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To evaluate bevacizumab pharmacokinetics and various dosing strategies for bevacizumab in pediatric patients. Methods: Data were collected from 232 pediatric patients (1971 concentrations) in 5 studies with a wide range of age (0.5 ~ 21 years), body weight (BWT, 5.9 ~ 125 kg) and regimens (5 ~ 15 mg/kg biweekly or triweekly). Data from 152 patients (1427 concentrations) and 80 patients (544 concentrations) were used for model-building and external validation, respectively. Steady-state exposure was simulated under BWT-based, BSA-based, IBW (ideal body weight)-based and Tier-based doses. NONMEM and R were used for analyses. Results: Typical estimates of clearance, central volume of distribution (V1) and median half-life were 9.04 mL/h, 2851 mL and 19.6 days, respectively. Clearance decreased with increasing albumin. Clearance and V1 increased with BWT and were higher in male patients. Clearance and V1 were lower children with primary CNS tumors than children with sarcomas, resulting in 49% higher trough (Cmin) and 29% higher peak concentration (Cmax). BWT-adjusted clearance and V1 remained unchanged across ages. Pediatric Cmin was similar to adult Cmin under all dosing strategies. Pediatric Cmax exceeded adult Cmax under Tier-based doses. Conclusions: BWT-adjusted pharmacokinetic parameter estimates in pediatric patients were similar to those in adults, and similar across ages. Bevacizumab exposure was higher in children with primary CNS tumors than children with sarcomas. BSA-based, IBW-based and Tier-based doses offered no substantial advantage over BWT-based dose currently used in adults for bevacizumab. Given the similarity in pharmacokinetics among many monoclonal antibodies, this may help develop practical pediatric dosing guidelines for other therapeutic antibodies.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12778
  • British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12776
  • [Show abstract] [Hide abstract]
    ABSTRACT: Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs may also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This may also be the case for some BBs. Peak toxicity may be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole bowel irrigation may mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings to improve myocardial contractility and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in treatment of vasodilatory shock. Optimising serum calcium concentration may confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which may limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12763
  • Article: Olaparib
    [Show abstract] [Hide abstract]
    ABSTRACT: Olaparib is used to treat BRCA-associated, platinum-sensitive ovarian cancer. Olaparib inhibits poly(ADP-ribose) polymerase, thereby blocking the repair of single strand DNA breaks. This results in synthetic lethality in BRCA-associated cancer cells, which have a dysfunction of another DNA repair pathway: homologous recombination.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12761
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review summarizes current knowledge about glucagon-like peptide 1 receptor agonists (GLP-1 RA) and their effects on bone metabolism and fracture risk. Recent in vivo and in vitro experiments indicated that GLP-1 RA could improve bone metabolism. GLP-1 could affect fat-bone axis by promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone mesenchymal precursor cells (BMSCs), which express GLP-1 receptor. GLP-1 RA may also influence the balance between osteoclasts and osteoblast, thus lead to more bone formation and less bone resorption. Wnt/β-catenin signaling is involved in this course. Mature osteocytes, which also express GLP-1 receptor, produce sclerostin which inhibits Wnt/β-catenin signaling by binding to low-density lipoprotein receptor-related protein (LRP) 5 and preventing the binding of Wnt. GLP-1 RA also decreases the expression of SOST/sclerostin and circulating levels of sclerostin. In addition, GLP-1 receptors are expressed in thyroid C cells, where GLP-1 induces calcitonin release and thus indirectly inhibits bone resorption. Furthermore, GLP-1 RA influences the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand (RANKL) /receptor activator of nuclear factor-κB (RANK) system by increasing OPG gene expression, thus reverses the decreased bone mass in rats models. However, a recent Meta-analysis and a cohort study did not show a significant relationship between GLP-RA use and fracture risk. Future clinical trials will be necessary to deeply investigate the relationship between GLP-1 RA use and fracture risk in diabetic patients.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12777
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIMThe objective of this study was to investigate whether the pharmacokinetics of orally administered levofloxacin show 24-hour variation. Levofloxacin was used as a model compound for solubility- and permeability-independent absorption and passive renal elimination.METHODS In this single centre, cross-over, open label study, twelve healthy subjects received an oral dose of 1000 mg levofloxacin at six different time-points equally divided over the 24-hour period. Population pharmacokinetic modelling was used to identify potential 24-hour variation in the pharmacokinetic parameters of this drug.RESULTSThe pharmacokinetics of levofloxacin could be described by a one-compartment model with first-order clearance and a transit compartment to describe drug absorption. The fit of the model was significantly improved when the absorption rate constant was described as a cosine function with a fixed period of 24 hours, a relative amplitude of 47% and a peak around 8:00 in the morning. Despite this variation in absorption rate constant, simulations of a once-daily dosing regimen show that Tmax, Cmax and the area under the curve at steady state are not affected by the time of drug administration.CONCLUSION The finding that the absorption rate constant shows considerable 24-hour variation may be relevant for drugs with similar physicochemical properties as levofloxacin that have a narrower therapeutic index. Levofloxacin, however, can be dosed without taking into account the time of day, at least in terms of its pharmacokinetics. This article is protected by copyright. All rights reserved.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12783
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimsA meta-analysis was performed to compare the therapeutic outcomes in patients treated for heart failure (HF) with recombinant human brain natriuretic peptide (rhBNP) and dobutamine.Methods PubMed, Embase and Chinese Biomedical Database were exhaustively searched to identify studies relevant to this meta-analysis. Eight cohort studies were found suitable for inclusion. Data regarding trial validity, methodological processes and clinical outcomes were extracted.ResultsPatients treated with rhBNP showed statistically significant reduction of in-hospital mortality and readmission rates compared to the dobutamine treated patient group (both P < 0.05). Further, rhBNP treated patient group showed higher survival outcomes, compared to dobutamine treated patients, when the post-treatment follow-up period was longer than 6 months (P < 0.05). Stratified analysis based on ethnicity showed a dramatic decrease of in-hospital mortality among mixed-race HF patients receiving rhBNP treatment (P < 0.05), but such decreases were not statistically significant in Asian and Caucasian populations (both P > 0.05). On the other hand, readmission rates were significantly lower in rhBNP treated Caucasian and mixed-race populations (both P < 0.05). Notably, in rhBNP treated group, dose levels of 0.015 and 0.03 incrementally lowered the readmission rates, displaying dose effect, and the readmission rates at both rhBNP doses were significantly lower than the dobutamine treated group (both P < 0.05).Conclusions Our meta-analysis results suggested that rhBNP therapy is associated with lower in-hospital mortality and readmission rates in HF patients compared to the dobutamine regimen. Nevertheless, large-scale prospective, randomized trials are necessary to confirm these findings.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12788
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To assess the effects of the changes in management of paracetamol overdose recommended by the UK Commission for Human Medicines on rates of hospital admission.Methods An interrupted time series analysis on data for hospital admissions for paracetamol poisoning for England between January 2010 and June 2014, and for Scotland between January 2010 and Sept 2014.Main Outcome MeasuresAdmissions to hospital with paracetamol poisoning (T39.1) as defined by 1st position coding in children and adults.ResultsThe time series analysis (Jan 2010 to June 2014) shows that admission rates for paracetamol poisoning were steady from 2010 to the date of change (Sept 2012), with an estimated 269 (95%CI 252.5-285.5) child (0-14 y) and 3541 (3454-3628) adult admissions per month. In September 2013, 12 months after the change, there were an estimated additional 116 (37.3% [17.2-67.4]) child and 426 (12.5% [4.5-19.6]) adult admissions. Thus in the year before the change (Sept 2011-Aug 2012) there were 45,181 (3,500 child: 41,681 adult), and in the year after (Sept 2012-Aug 2013) there were 50,198 admissions (4,779 child: 45,419 adult). The overall proportion of child admissions was significantly greater after the change (Chi squared 32.486, p < 0.001), emphasising the disproportionate effect in children.Conclusions Changes to the management guidelines for paracetamol poisoning in September 2012 were rapidly implemented, but have particularly increased paediatric hospital admissions for paracetamol poisoning. This impact in children, who are at low risk of mortality from paracetamol toxicity appears excessive.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12779
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimsIntrathecal baclofen (ITB) has proven to be an effective and safe treatment for severe spasticity. However, although ITB is used extensively, clinical decisions are based on very scarce pharmacokinetic-pharmacodynamic (PKPD) data. The aim of this study was to measure baclofen CSF concentrations and clinical effects after administration of various ITB boluses in patients with spasticity and to create a PKPD model for ITB.Methods Twelve patients with severe spasticity received four different bolus doses of ITB (0, 25, 50, 75 µg and an optional dose of 100 µg), administered via a catheter with the tip at thoracic level (Th) 10. After each bolus, ten CSF samples were taken at fixed time intervals, using a catheter with the tip located at Th12. Clinical effect was assessed by measuring spasticity with the Modified Ashworth Scale (MAS). These data were used to develop a PKPD model.ResultsAll patients achieved an adequate spasmolytic effect with ITB doses varying from 50-100 µg. No serious side-effects were observed. CSF baclofen concentrations, as well as the clinical effects, correlated significantly with ITB doses. The PK model predicted a steep spinal concentration gradient of ITB along the spinal axis. The clinical effect could be predicted using a delayed-effect model.ConclusionsITB is an effective and safe therapy, however, with a steep concentration gradient along the spinal axis. This means that the administered baclofen is staying mainly around the catheter tip, which stresses the importance to position the ITB catheter tip closely to the targeted spinal level.
    British Journal of Clinical Pharmacology 09/2015; DOI:10.1111/bcp.12781