European Journal of Clinical Pharmacology (EUR J CLIN PHARMACOL)

Publisher: Springer Verlag

Journal description

The European Journal of Clinical Pharmacology publishes original papers short communications and letters to the editors on all aspects of clinical pharmacology and drug therapy in humans. Data from animal experiments are accepted only in the context of parallel experiments in man reported in the same paper. The Journal also accepts review articles on special problems related to these areas and encourages debate on controversial issues.

Current impact factor: 2.70

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.697
2012 Impact Factor 2.741
2011 Impact Factor 2.845
2010 Impact Factor 3.032
2009 Impact Factor 2.743
2008 Impact Factor 2.497
2007 Impact Factor 2.177
2006 Impact Factor 2.029
2005 Impact Factor 2.298
2004 Impact Factor 2.083
2003 Impact Factor 1.972
2002 Impact Factor 1.955
2001 Impact Factor 1.922
2000 Impact Factor 1.729
1999 Impact Factor 1.771
1998 Impact Factor 1.42
1997 Impact Factor 1.219
1996 Impact Factor 1.308
1995 Impact Factor 1.233
1994 Impact Factor 1.038
1993 Impact Factor 1.006
1992 Impact Factor 1.204

Impact factor over time

Impact factor

Additional details

5-year impact 2.96
Cited half-life 8.60
Immediacy index 0.68
Eigenfactor 0.01
Article influence 0.81
Website European Journal of Clinical Pharmacology website
Other titles European journal of clinical pharmacology (Online), EJCP, Eur j clin pharmacol
ISSN 0031-6970
OCLC 41916239
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's pre-print on pre-print servers such as
    • Author's post-print on author's personal website immediately
    • Author's post-print on any open access repository after 12 months after publication
    • Publisher's version/PDF cannot be used
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Overdose with baclofen, a derivative of the inhibitory neurotransmitter γ-aminobutyric acid, may lead to severe respiratory and central nervous system depression and can be life-threatening. Prolonged half-lives of baclofen, of up to 34 h, have been reported in patients after overdose. Hemodialysis has proven to be a successful approach to improve clearance of baclofen, but the value of continuous venovenous hemofiltration (CVVH) is unclear. We applied CVVH in a patient with acute baclofen overdose. Methods Pharmacokinetic measurements of baclofen in serum and hemofiltrate were made at six time points after hospital admission. Baclofen concentration-time data were analyzed using non-compartmental methods, and the relative contribution of clearance by hemofiltration to total baclofen clearance was calculated. Results Baclofen concentrations in serum varied between 1.81 and 0.05 mg/L. Concentrations of baclofen in hemofiltrate were within the same range (between 0.74 and 0.05 mg/L), and the elimination half-life during hemofiltration was estimated at 4.8 h. Total clearance and clearance via hemofiltration were estimated at 6.6 and 2.4 L/h, indicating that clearance could be increased by approximately 57 % by applying hemofiltration. Conclusions The presented case demonstrates the usefulness of CVVH in the treatment of baclofen overdose and indicates that CVVH can be used as an alternative to hemodialysis in patients with overdose of baclofen.
    European Journal of Clinical Pharmacology 01/2015; 71(3). DOI:10.1007/s00228-014-1802-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Tramadol is widely used for acute, chronic, and neuropathic pain. Its primary active metabolite is O-desmethyltramadol (M1), which is mainly accountable for the μ-opioid receptor-related analgesic effect. Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor). Methods We used a randomized placebo-controlled crossover study design with 12 healthy subjects, of which 8 were extensive and 4 were ultrarapid CYP2D6 metabolizers. On the pretreatment day 4 with terbinafine (250 mg once daily), itraconazole (200 mg once daily) or placebo, subjects were given tramadol 50 mg orally. Plasma concentrations of tramadol and M1 were determined over 48 h and some pharmacodynamic effects over 12 h. Pharmacokinetic variables were calculated using standard non-compartmental methods. Results Terbinafine increased the area under plasma concentration–time curve (AUC0-∞) of tramadol by 115 % and decreased the AUC0-∞ of M1 by 64 % (P Terbinafine increased the peak concentration (C max) of tramadol by 53 % (P C max of M1 by 79 % (P P Terbinafine reduced subjective drug effect of tramadol (P Itraconazole had minor effects on tramadol pharmacokinetics. Conclusions Terbinafine may reduce the opioid effect of tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole has no meaningful interaction with tramadol in subjects who have functional CYP2D6 enzyme.
    European Journal of Clinical Pharmacology 01/2015; 71(3). DOI:10.1007/s00228-014-1799-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the effects of food on the pharmacokinetics of sublingual asenapine. Healthy male volunteers (n = 26, age 19-53 years) randomly received a single sublingual dose of asenapine 5 mg after ≥10 h fasting (Treatment A, reference), after a high-fat meal (Treatment B) and after ≥10 h fasting with a high-fat meal at 4 h post-dose (Treatment C). Blood samples were drawn over 72 h to measure asenapine plasma concentrations. Effects of food intake on asenapine pharmacokinetics were assessed using bioequivalence criteria and evaluated using a compartmental modelling analysis. Compared with the reference, mean asenapine exposure (AUC0-last and AUC0-∞) was approximately 20 % lower after intake of a high-fat meal prior to dosing, whereas Cmax decreased by only about 10 %. When a high-fat meal was taken 4 h post-dose in the fasting state, asenapine concentrations were similar to the reference during the first 4 h post-dose. After the meal intake, asenapine concentrations decreased quickly for several hours. Compartmental modelling indicated that a transient 2.5-fold increase in asenapine clearance after eating could explain the asenapine concentration-time profiles for both food regimens. To our knowledge, this is the first study investigating the effect of food upon the sublingual administration of a drug. A high-fat meal taken before or 4 h post-dose of sublingual asenapine indirectly caused a transient increase in liver blood flow that resulted in a temporal increase in asenapine clearance. As the effects on asenapine exposure were small and not clinically relevant, no additional restrictions are required for the timing of food intake in relation to asenapine dosing.
    European Journal of Clinical Pharmacology 01/2015; 71(1):65-74. DOI:10.1007/s00228-013-1587-4
  • [Show abstract] [Hide abstract]
    ABSTRACT: N(1)-methylnicotinamide (NMN) was proposed as an in vivo probe for drug interactions involving renal cation transporters, which, for example, transport the oral antidiabetic drug metformin, based on a study with the inhibitor pyrimethamine. The role of NMN for predicting other interactions with involvement of renal cation transporters (organic cation transporter 2, OCT2; multidrug and toxin extrusion proteins 1 and 2-K, MATE1 and MATE2-K) is unclear. We determined inhibition of metformin or NMN transport by trimethoprim using cell lines expressing OCT2, MATE1, or MATE2-K. Moreover, a randomized, open-label, two-phase crossover study was performed in 12 healthy volunteers. In each phase, 850 mg metformin hydrochloride was administered p.o. in the evening of day 4 and in the morning of day 5. In phase B, 200 mg trimethoprim was administered additionally p.o. twice daily for 5 days. Metformin pharmacokinetics and effects (measured by OGTT) and NMN pharmacokinetics were determined. Trimethoprim inhibited metformin transport with K i values of 27.2, 6.3, and 28.9 μM and NMN transport with IC50 values of 133.9, 29.1, and 0.61 μM for OCT2, MATE1, and MATE2-K, respectively. In the clinical study, trimethoprim increased metformin area under the plasma concentration-time curve (AUC) by 29.5 % and decreased metformin and NMN renal clearances by 26.4 and 19.9 %, respectively (p ≤ 0.01). Moreover, decreases of NMN and metformin renal clearances due to trimethoprim correlated significantly (r S = 0.727, p = 0.010). These data on the metformin-trimethoprim interaction support the potential utility of N(1)-methylnicotinamide as an endogenous probe for renal drug-drug interactions with involvement of renal cation transporters.
    European Journal of Clinical Pharmacology 01/2015; 71(1):85-94. DOI:10.1007/s00228-014-1770-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to assess the impact of clinical characteristics and management on the mid- to long-term follow-up prognosis of unselected over-80-year-old patients hospitalized for a first heart failure (HF) episode in a real-life setting. Despite the increasing proportion of HF patients over 80 years of age, the latter remain a poorly studied population. Analysis was based on the EGB ("Echantillon Généraliste des Bénéficiaires") database. A cohort comprising 1825 adult patients with a first admission for HF between 2009 and 2011 was created and followed until June 2013 for survival analysis. Over-80-year-old patients represented 53 % of this cohort, with a median follow-up of 18.6 (3.3-29.5) months. Only 5 % of patients over 80 years received an optimal treatment at discharge [combination of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA)]. During the follow-up period, only BB prescription levels (p = 0.02) increased. In over-80-year-olds, in-hospital mortality was 12 % (range, 10-14) and survival was 62.8 % (59.6-65.7) and 48.7 % (45.4-51.9) at 12 and 24 months, respectively. On multivariate analysis, dyslipidemia [0.74 (0.58-0.94), p = 0.02], vitamin K antagonists [0.55 (0.44-0.69), p < 0.001], ACEi/ARB + BB + MRA [0.56 (0.32-0.96), p = 0.04], and ACEi/ARB + BB [0.57 (0.45-0.72), p < 0.001] were associated with improved survival, conversely to cardiogenic shock [3.37 (1.90-5.98), p < 0.001], denutrition [1.61 (1.24-2.09), p < 0.001], and age over 90 [1.35 (1.09-1.67), p = 0.01]. These real-life HF data provide insight into prognostic factors and demonstrate that over-80-year-old HF patients displaying several comorbidities are poorly managed, despite the confirmed clinical benefit of HF drugs.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1794-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical trials have shown that evidence-based secondary prevention medications reduce mortality after acute myocardial infarction (AMI). Yet, these medications are generally underused in daily practice, and older people are often excluded from drug trials. The purpose of this study was to examine whether the relationship between adherence to evidence-based drugs and post-AMI mortality varies with increasing age. The study population was defined as all residents in the Local Health Authority of Bologna (Italy) hospitalized for AMI between January 1, 2008 and June 30, 2011, and followed up until December 31, 2012. Medication adherence was calculated as the proportion of days covered (PDC) for filled prescriptions of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, antiplatelet drugs, and statins; patients were classified as adherent (PDC ≥75 %) or nonadherent (PDC <75 %). We used incidence density sampling, and the moderating effect of age on the relationship between adherence and mortality was investigated through conditional multiple logistic regression analysis. The study population comprised 3963 patients. During the 5-year study period, 1085 deaths (27.4 %) were observed. For both younger and older patients, adherence to polytherapy (three or four medications) was associated with lower mortality (adj. rate ratio = 0.41; P < 0.001). A significant inverse relationship was found between adherence to each of the four medications and mortality, although the risk reduction associated with antiplatelet therapy declined after the age of 70-75. The beneficial effect of evidence-based polytherapy on mortality following AMI is observed also in older populations. Nevertheless, the risk-benefit ratio associated with antiplatelet therapy is less favorable with increasing age.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1793-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors. Methods Patients receiving acenocoumarol maintenance therapy (n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method. Results The mean daily acenocoumarol maintenance dose was found to be 3.7 ± 2.3 (SD) mg/day. The CYP2C9 *1*2, CYP2C9 *1*3, and CYP2C9 *2*3 variant genotypes significantly reduced the dose by 56.7 % (2.0 mg), 67.6 % (1.6 mg), and 70.3 % (1.5 mg) than wild-type carriers 4.1 mg, p CYP2C9 and GGCX (rs11676382) were found to be associated with lower acenocoumarol dose, whereas CYP4F2 (rs2108622) was associated with higher doses. Age, body mass index (BMI), variation of CYP2C9, VKORC1, CYP4F2, and GGCX were the major determinants of acenocoumarol maintenance dose, accounting for 61.8 % of its variability (adjusted r 2 = 0.615, p VKORC1 variants, rs9923231 alone contributed up to 28.6 % of the acenocoumarol dose variation. Conclusion VKORC1 rs9923231 polymorphism had the highest impact on acenocoumarol daily dose. A new pharmacogenetic algorithm was established to determine the acenocoumarol dose in South Indian population.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1791-x
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin 18 (IL-18) is a potent proinflammatory cytokine thought to down-regulate cytochrome P450 (CYP) enzyme activities. This study aimed to assess the potential influence of two functional single nucleotide polymorphisms (SNPs) in the IL-18 promoter region on the tacrolimus pharmacokinetics in Chinese renal transplant patients. We enrolled 96 renal allograft recipients receiving tacrolimus-based immunosuppressive regiments. Two functional SNPs in the IL-18 gene promoter region at the positions -137G/C (rs187283) and -607A/C (rs1946518) and one SNP (rs776746) of CYP3A5 were genotyped using a Mass ARRAY platform. Tacrolimus daily doses (mg/day) and trough tacrolimus concentration (ng/ml) were continuously recorded for 1 month after transplantation. The tacrolimus C/D ratio was significantly associated with the IL-18 rs1946518 gene polymorphism in the first month after transplantation (P = 0.0225). We studied the influence of its polymorphism on tacrolimus C/D ratios in subjects with different CYP3A5 genotype backgrounds, and among patients with CYP3A5 expressers, the difference among the three genotypes was even more striking (P < 0.001). We did not find significant differences in tacrolimus C/D ratios between the IL-18 rs187238 genotypes, either nominally or according to the CYP3A5 genotype. In a simple linear regression model, age, hemoglobin (Hb), CYP3A5 gene polymorphisms, and IL-18 A-607C gene polymorphisms were associated with log-transformed tacrolimus C/D ratios (P < 0.05). In the final multiple linear regression model, CYP3A5 polymorphisms were the most important variant, accounting for 19.5 % of total variation involved in tacrolimus pharmacokinetics. Our findings suggest that a combined analysis of CYP3A5 and IL-18 promoter polymorphisms may help clinicians develop individualized tacrolimus treatment, which is based on determining CYP3A5 genotype.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1785-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over-the-counter combinations containing acetaminophen and phenylephrine for treatment of the common cold and influenza are widespread, but there are few data about pharmacokinetics of these two drugs used in combination. We aimed to investigate pharmacokinetic interactions between acetaminophen and phenylephrine. A series of four randomised, open-label, crossover studies investigating phenylephrine and acetaminophen combination pharmacokinetics were undertaken (n = 28, 30, 6 and 26) using standard non-compartmental analyses. Time-concentration observations from these four studies were pooled to examine the interaction between these two compounds. Data were analysed using non-linear mixed effects models. Non-compartmental analyses showed an approximate doubling of phenylephrine plasma concentration when the standard 10-mg dose was administered in combination with acetaminophen. Population analysis was based on data from 90 subjects with 2050 observations. The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %. When combined with 500 mg of acetaminophen, bioavailability increased by 64 % (Fbio 1.64). Phenylephrine 5 mg in combination with acetaminophen 1000 mg produced a phenylephrine plasma time-concentration profile similar to that seen with phenylephrine 10 mg administered alone. The relative bioavailability of phenylephrine was increased when co-administered with acetaminophen.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1788-5
  • [Show abstract] [Hide abstract]
    ABSTRACT: Periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) has received great attention due to its significant association with mortality and morbidity. Accordingly, cardioprotection during PCI is one of the important therapeutic concerns. Regarding the potential cardiovascular benefits of pentoxifylline this study was performed to evaluate whether the pretreatment pentoxifylline could reduce PMI in patients who are undergoing elective PCI. A randomized clinical trial on 85 patients undergoing elective PCI was performed. The intervention group (n = 41) received 1200 mg pentoxifylline in divided doses plus the standard treatment before PCI, while the control group (n = 44) received the standard treatment. For assessing myocardial damage during PCI, the levels of CK-MB and troponin-I were measured at baseline, 8, and 24 h after the procedure. Then, patients were followed up for a 1-month period regarding the major adverse cardiac effect. Comparing with the control group, no significant change of CK-MB at 8 (p = 0.315) and 24 h (p = 0.896) after PCI was documented in pentoxifylline group. Similarly, no significant change was found in troponin-I at 8 (p = 0.141) and 24 h (p = 0.256) after PCI. This study could not support the pretreatment with pentoxifylline in the prevention of PMI in patients undergoing elective PCI. However, the trend was toward the potential benefit of pentoxifylline.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1782-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.
    European Journal of Clinical Pharmacology 12/2014; 71(2). DOI:10.1007/s00228-014-1787-6
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prescription drug abuse and dependence is a widespread phenomenon in many countries. The use of disproportionality measures in drug abuse surveillance is rarely performed. The aim of this study is to determine the occurrence of signals of abuse and dependence for different psychoactive drugs in real-life settings. Disproportionality analysis was realised from a database specifically constructed for the monitoring of drug abuse and dependence. This database provides information on approximately 5000 patients and 8000 consumption modalities for more than 100 distinct psychoactive medications for 2010 and 2011. Proportional reporting ratio (PRR) was computed in two population groups: subjects under an opiate maintenance treatment (OMT) versus those not under OMT, and focused on four types of behaviours: abuse and dependence, illegal acquisition, diverted route of administration and concomitant alcohol use. Among the 100 psychoactive drugs for which a signal could be detected, those presenting the highest signals were the following: flunitrazepam, clonazepam, methylphenidate, ketamine, morphine sulfate, codeine and buprenorphine. The present study shows an innovative application of disproportionality measures for drug abuse monitoring based on two cross-national, annual studies. The disproportionality analysis provided the opportunity to reveal and compare the magnitude of signals between 100 psychoactive drugs. This approach helps to compare the magnitude of abuse and dependence behaviours for a large number of drugs, and allows prioritizing actions in a context where such events are usually underreported.
    European Journal of Clinical Pharmacology 11/2014; 71(2). DOI:10.1007/s00228-014-1783-x
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antidepressant therapy is associated with disturbances in glucose homeostasis, and hypoglycemia is most pronounced in antidepressants with a high affinity for a serotonin reuptake transporter such as fluoxetine and sertraline [1, 2]. In the therapeutic use of venlafaxine, a dual-acting serotonin and norepinephrine reuptake inhibitor, no hypoglycemia has been demonstrated as yet. However, there are two case reports of severe hypoglycemia in venlafaxine overdose that were explained by increased insulin levels [3, 4]. In this case, we present prolonged hypoglycemia with normal insulin levels in venlafaxine overdose.A 42-year-old woman weighting 70 kg with a history of depression treated with venlafaxine was admitted to the Emergency Department 4 h following ingestion of 9.0 g of venlafaxine in a suicide attempt. On arrival, she was somnolent and had mydriasis, tremor and tachycardia. The initial serum glucose level was 2.6 mmol/L; all other laboratory results, including liver and kidney t ...
    European Journal of Clinical Pharmacology 11/2014; 71(2). DOI:10.1007/s00228-014-1784-9
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the 1970s, the use of metamizole is controversial due to the risk of agranulocytosis. The aim of this study was to analyze individual case safety reports (ICSRs) of metamizole-associated hematological adverse drug reactions (ADRs).
    European Journal of Clinical Pharmacology 11/2014; 71(2). DOI:10.1007/s00228-014-1781-z
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to investigate if the prescription of proton-pump inhibitors (PPIs) was associated with a sudden risk of acute myocardial infarction (AMI) while controlling for time-invariant confounding by using a case-crossover design. An association might indicate that physicians take prodromal symptoms of myocardial ischaemia for dyspepsia.
    European Journal of Clinical Pharmacology 11/2014; DOI:10.1007/s00228-014-1779-6