Clinical Drug Investigation (CLIN DRUG INVEST)

Journal description

Clinical Drug Investigation gives you rapid access to the best designed, peer reviewed clinical and pharmacoeconomic studies worldwide, allowing you to keep up to date with the latest original research in this exciting area. The Journal's aim is rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. This includes clinical trials, outcomes research, clinical pharmacoeconomic studies, pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs, clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice and, in some instances, pharmacodynamic or pharmacokinetic studies in healthy volunteers, but in which some established or purported implications for clinical prescribing are discussed. In addition, short communications and case study reports that meet these criteria are also encouraged, as are letters to the editor.

Current impact factor: 1.70

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 1.704
2012 Impact Factor 1.915
2011 Impact Factor 1.822
2010 Impact Factor 1.622
2009 Impact Factor 1.414
2008 Impact Factor 1.301

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.64
Cited half-life 4.90
Immediacy index 0.36
Eigenfactor 0.00
Article influence 0.43
Website Clinical Drug Investigation website
ISSN 1179-1918
OCLC 31920475
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Publications in this journal

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    ABSTRACT: Nondisabling cerebrovascular events represent the largest group of cerebrovascular disease with a high risk of recurrent stroke. A recent trial demonstrated that dual-antiplatelet therapy (clopidogrel and aspirin), compared with aspirin monotherapy, reduced the risk of recurrent stroke and was not associated with increased risk of hemorrhagic events. Apixaban, a new oral anticoagulant, has been proven to be as safe and effective as traditional anticoagulants while carrying significantly less risk of intracranial hemorrhage. Patients with transient ischemic attack (TIA)/minor stroke might benefit from apixaban treatment; therefore, an adequately powered randomized study is needed.
    Clinical Drug Investigation 09/2014; 34(11). DOI:10.1007/s40261-014-0228-8
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    ABSTRACT: This study examined the effects of moderate renal impairment on the pharmacokinetics and pharmacodynamics of canagliflozin in Japanese patients with type 2 diabetes mellitus.
    Clinical Drug Investigation 09/2014; 34(10). DOI:10.1007/s40261-014-0226-x
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    ABSTRACT: Edoxaban is a novel direct inhibitor of activated factor Xa. A previous human pharmacokinetic study suggested a less than proportional increase in edoxaban exposure at higher dose concentrations, but the quantitative relationship, including the point of inflection, has not yet been fully characterized. The objectives of this analysis were to characterize the population pharmacokinetics and quantify the dose-exposure relationship of edoxaban over a dose range of 10-180 mg. Concentration data from 278 subjects in five phase I clinical studies were used to perform a population pharmacokinetic analysis using non-linear mixed-effects modeling. Model performance was assessed by standard goodness-of-fit diagnostic plots, visual predictive check, and bootstrapping procedures. Edoxaban pharmacokinetics were described by a two-compartment model, with first-order absorption preceded by a lag time for absorption (t (lag)). Edoxaban relative bioavailability (F (1)) was estimated as 67.2 % and remained constant at the dose range of 10-30 mg. For doses above 30 mg, every 30-mg dose increase was associated with an approximately 6.7 % decrease in F (1). Sex was identified as a significant covariate on clearance (CL), with female subjects showing 13.1 % lower CL than male subjects. Food was found to affect t (lag), but not F (1). When compared with the fasted state, administration of edoxaban with food prolonged t (lag) from 0.233 to 0.375 h. The population pharmacokinetic model provided an adequate description of the observed data. The analysis results suggested a less than proportional dose-exposure relationship for edoxaban at a dose above 30 mg. A statistically significant sex effect on CL and food effect on t (lag) were identified but are unlikely to be clinically important.
    Clinical Drug Investigation 09/2014; 34(10). DOI:10.1007/s40261-014-0229-7
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    ABSTRACT: Background and Objectives Administration of a loading dose of a statin (HMG-CoA reductase inhibitor) prior to percutaneous coronary intervention (PCI) contributes to protection from myocardial ischemic-reperfusion injury. This trial was designed to investigate the effect and mechanism of loading-dose rosuvastatin therapy before PCI in patients with acute coronary syndrome. Methods One hundred and forty-three patients with acute coronary syndrome were randomized to either the loading-dose (rosuvastatin 40 mg given 4 h before PCI) or conventional-dose (rosuvastatin 10 mg given 4 h before PCI) group. Blood samples were collected before and 0, 24, and 72 h post-PCI for measurement of serum cardiac troponin-I (cTn I), creatine kinase-MB (CK-MB), superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA). Echocardiography and the major adverse cardiac/cerebrovascular events (MACCE) rate were followed up for 6 months post-PCI. Results Blood serum CK-MB and cTn I were significantly lower in the loading-dose group than in the conventional-dose group at 24 and 72 h post-PCI [CK-MB: 26.90 +/- 3.22 vs. 32.96 +/- 2.65 IU/L, P = 0.024; 10.79 +/- 4.65 vs. 15.18 +/- 5.39 IU/L, P = 0.021. cTn I: 0.046 +/- 0.007 vs. 0.055 +/- 0.002 ng/mL, P = 0.015; 0.027 +/- 0.006 vs. 0.041 +/- 0.006 ng/mL, P = 0.026]. Echocardiography at 6 months after PCI revealed significant improvement in cardiac function in the loading-dose group compared with the conventional-dose group (P < 0.05). The MACCE rate at 6 months after PCI in the loading-dose group was lower than in the conventional-dose group (P = 0.0428). The levels of MDA and ROS were decreased and the SOD level was significantly higher in the loading-dose group than in the conventional-dose group at 0, 24, and 72 h post-PCI (P < 0.05). Conclusion Administration of loading-dose rosuvastatin in patients with acute coronary syndrome prior to PCI exerts myocardial protection by inhibition of oxidative stress.
    Clinical Drug Investigation 09/2014; 34(11). DOI:10.1007/s40261-014-0231-0
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    ABSTRACT: Evidence indicates that vitamin K antagonists (VKAs) and oral anticoagulant therapy are under-utilised for stroke prevention in patients with non-valvular atrial fibrillation (AF), and patients who decline or cannot tolerate such treatment are often prescribed aspirin instead. Apixaban has been shown in the AVERROES trial to be superior to aspirin in preventing stroke and systemic embolism without significantly increasing the risk of major bleeding among patients with AF who are unsuitable for VKA therapy. This study estimates the economic implications and potential cost effectiveness of apixaban compared with aspirin in such individuals from the perspective of healthcare payers in Belgium.
    Clinical Drug Investigation 08/2014; 34(10). DOI:10.1007/s40261-014-0224-z
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    ABSTRACT: In vitro studies have demonstrated that the aqueous solubility of the tyrosine kinase inhibitor ponatinib decreases as pH increases. The primary aim of this study was to assess the effects of the gastric proton pump inhibitor lansoprazole on the pharmacokinetics of ponatinib. The single-dose safety profile of ponatinib with and without coadministration of lansoprazole was also characterized. This was a phase I, open-label, non-randomized, two-period crossover study in 20 healthy subjects aged 18-55 years. Subjects received a single oral dose of ponatinib 45 mg alone on day 1, an oral dose of lansoprazole 60 mg on day 14, and ponatinib 45 mg plus lansoprazole 60 mg on day 15. Lansoprazole coadministration resulted in a 1-h increase in the time to maximum plasma concentration (t (max)) of ponatinib (6 vs. 5 h post-dose; P < 0.001). A corresponding 25 % decrease in the geometric mean maximum plasma concentration (C (max)) of ponatinib was observed for ponatinib + lansoprazole versus ponatinib alone (40.67 vs. 53.96 ng/mL). Importantly, lansoprazole did not decrease the overall ponatinib systemic exposure as assessed by the ponatinib area under the plasma concentration-time curve from time zero to infinity (AUC(a) 1,153 ng center dot h/mL for lansoprazole + ponatinib vs. 1,222 ng center dot h/mL for ponatinib alone). The safety profile was considered acceptable when ponatinib was administered alone or with lansoprazole. Although coadministration of lansoprazole led to a modest, albeit statistically significant, reduction in ponatinib C (max), overall systemic exposure to ponatinib did not change. The findings suggest that no dose adjustment is necessary when ponatinib is administered with drugs that increase gastric pH.
    Clinical Drug Investigation 08/2014; 34(10). DOI:10.1007/s40261-014-0225-y
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    ABSTRACT: The combination of direct-acting antiviral agents in patients with chronic hepatitis C virus (HCV) infection has demonstrated clinical benefit; however, evaluation of potential drug-drug interactions is required prior to therapy.
    Clinical Drug Investigation 08/2014; DOI:10.1007/s40261-014-0219-9
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    ABSTRACT: Pitavastatin is the latest statin to be approved and has shown beneficial effects on plasma lipid profiles. The aim of the present meta-analysis was to assess both the efficacy and safety of pitavastatin versus simvastatin, one of the most commonly used statins.
    Clinical Drug Investigation 07/2014; DOI:10.1007/s40261-014-0215-0
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    ABSTRACT: Latanoprost is an ester prodrug prostaglandin F2α analogue that is a selective agonist of endogenous prostanoid FP receptors and that reduces intraocular pressure (IOP) by increasing the uveoscleral outflow of aqueous humour. Preservative-free (PF) latanoprost [Monoprost(®)] is a new formulation of latanoprost that is approved for use in the EU in patients with primary open-angle glaucoma (POAG)/ocular hypertension. This article reviews the clinical pharmacology of this new formulation, focussing on its efficacy and tolerability in this indication. PF latanoprost was efficacious in reducing IOP in a randomized, investigator-masked, multinational trial in patients with POAG/ocular hypertension (n = 404). At days 15, 42 and 84 of follow-up, PF latanoprost was noninferior to benzalkonium chloride-preserved (BAK) latanoprost in terms of reductions in IOP. In this trial, at days 42 and 84 the proportions of patients with conjunctival hyperaemia were significantly lower with PF latanoprost than with BAK latanoprost. Patient subjective ratings of ocular symptoms were also significantly lower with PF latanoprost than with BAK latanoprost. In the absence of head-to-head comparisons with other anti-glaucoma drugs, an adjusted, indirect comparison meta-analysis was performed using data from 21 randomized clinical trials in patients with POAG/ocular hypertension. Based on this analysis, PF latanoprost had similar efficacy to different formulations of three comparator prostaglandin analogues in reducing the patient's IOP and was associated with a significantly lower risk of developing hyperaemia/ocular redness than these comparators. PF latanoprost offers a useful alternative to the available preserved prostaglandin analogues for the treatment of POAG/ocular hypertension.
    Clinical Drug Investigation 06/2014; 34(7). DOI:10.1007/s40261-014-0203-4
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    ABSTRACT: Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of pulmonary arterial hypertension (PAH). Warfarin, an anticoagulant often prescribed to patients with PAH, has a narrow therapeutic index and is prone to potential interactions with drugs. This study assessed the effects of macitentan on the pharmacokinetics and pharmacodynamics of single-dose warfarin in healthy subjects. This was a randomised, open-label, single-centre, two-way crossover (treatment A followed by treatment B, or vice versa), phase I study in 14 healthy male subjects. Treatment A was a loading dose of macitentan 30 mg on Day 1 followed by 10 mg once daily for 8 days, with a single 25 mg dose of warfarin on Day 4. Treatment B was a single dose of warfarin on Day 1. Blood samples were assessed for warfarin pharmacokinetics (R- and S-warfarin) and pharmacodynamics [international normalised ratio (INR) and factor VII]. Plasma trough concentrations of macitentan and its active metabolite (ACT-132577) and the safety and tolerability of each treatment were also assessed. Plasma concentrations of R- and S-warfarin were similar in both treatment periods. Warfarin did not affect the mean trough plasma concentrations of macitentan or ACT-132577. Macitentan did not affect the pharmacodynamics of warfarin; the mean INR and factor VII activity versus time profiles were similar with and without macitentan. The absence of effect of macitentan on the pharmacokinetics and pharmacodynamics of a single dose of warfarin suggests that both drugs can be concomitantly administered without need for dose adjustment.
    Clinical Drug Investigation 05/2014; 34(8). DOI:10.1007/s40261-014-0207-0
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    ABSTRACT: The treatment of hyperlipidaemia in human immunodeficiency virus (HIV)-infected patients has become increasingly important. However, treatment options are limited because of the drug-drug interaction between certain statins and HIV medications metabolized by cytochrome P450 (CYP) enzymes. The primary objective was to investigate the steady-state pharmacokinetics of pitavastatin when co-administered with darunavir/ritonavir. The secondary objective was to investigate the steady-state pharmacokinetics of both darunavir and ritonavir when co-administered with pitavastatin. This was a single-centre, open-label, multi-dose, fixed-sequence study in HIV seronegative healthy volunteers. Pitavastatin 4 mg was administered once daily on days 1-5 and on days 12-16, and darunavir 800 mg/ritonavir 100 mg once daily on days 6-16. Pharmacokinetic blood sampling was performed on days 5, 11 and 16. No significant interaction was concluded if the 90 % confidence intervals (CIs) of the geometric mean ratios (GMRs) for total exposure [i.e. the area under the plasma concentration-time curve over a dosing interval at steady state (AUC0-τ )] and for peak exposure [i.e. the maximum plasma concentration (C max)] of the two treatments were within the 80-125 % range. Twenty-eight subjects (mean age 30.5 years) were enrolled, and pharmacokinetic data were available for 27 subjects. For pitavastatin, the GMRs and 90 % CIs for the AUC0-τ and C max ratios with co-administration were 0.74 (0.69-0.80) and 0.96 (0.84-1.09), respectively. For both darunavir and ritonavir, the 90 % CIs for the AUC0-τ and C max ratios were within 80-125 % with pitavastatin co-administration. No significant safety issues were reported. Darunavir/ritonavir decreased total exposure to pitavastatin by 26 %, while peak exposures were similar. Pitavastatin did not influence the pharmacokinetics of darunavir or ritonavir. There is limited interaction between pitavastatin and darunavir/ritonavir.
    Clinical Drug Investigation 05/2014; 34(7). DOI:10.1007/s40261-014-0198-x
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    ABSTRACT: In patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), posaconazole has been proven more effective in the prevention of invasive fungal infection (IFI) than fluconazole or itraconazole (standard azoles) The current analysis seeks to estimate the cost effectiveness of prophylactic posaconazole compared with standard azoles in AML or MDS patients with severe chemotherapy-induced neutropenia in Sweden. A decision-analytic model was used to estimate life expectancy, costs, and quality-adjusted life-years (QALYs). Efficacy data were derived from a phase III clinical trial. Life expectancy and quality of life data were collected from the literature. A modified Delphi method was used to gather expert opinion on resource use for an IFI. Unit costs were captured from hospital and pharmacy pricelists. A probabilistic sensitivity analysis (PSA) was used to investigate the impact of uncertainty in the model parameters on the cost-effectiveness results. The estimated mean direct cost per patient with posaconazole prophylaxis was 46,893 Swedish kronor (SEK) ( 5,387) and SEK50,017 ( 5,746) with standard azoles. Prophylaxis with posaconazole resulted in 0.075 QALYs gained compared with standard azoles. At a cost-effectiveness threshold of SEK500,000/QALY the PSA demonstrated a more than 95 % probability that posaconazole is cost effective versus standard azoles for the prevention of IFI in high-risk neutropenic patients in Sweden. Given the assumptions, methods, and data used, posaconazole is expected to be cost effective compared with standard azoles when used as antifungal prophylaxis in AML or MDS patients with chemotherapy-induced prolonged neutropenia in Sweden.
    Clinical Drug Investigation 05/2014; DOI:10.1007/s40261-014-0199-9
  • Clinical Drug Investigation 05/2014; 34(6). DOI:10.1007/s40261-014-0201-6