Clinical Drug Investigation (CLIN DRUG INVEST)

Publisher: Springer Verlag

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: 1.56

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 1.557
2013 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
2007 Impact Factor 0.602
2006 Impact Factor 0.559
2005 Impact Factor 0.707
2004 Impact Factor 0.77
2003 Impact Factor 0.709
2002 Impact Factor 0.914
2001 Impact Factor 0.846
2000 Impact Factor 0.888
1999 Impact Factor 0.651
1998 Impact Factor 0.71
1997 Impact Factor 0.913

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.61
Cited half-life 4.90
Immediacy index 0.61
Eigenfactor 0.00
Article influence 0.45
Website Clinical Drug Investigation website
ISSN 1179-1918
OCLC 31920475
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
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  • Conditions
    • Author's pre-print on pre-print servers such as arXiv.org
    • 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: Background and objectives: Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Methods: Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. Results: In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. Conclusions: The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.
    No preview · Article · Jan 2016 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). Methods: Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased ≥0.1 mmol/L, unchanged ±0.1 or ≥0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. Results: HDL-C decreased in 20 %, was unchanged in 58%, and increased in 22 % of patients initiated on statin treatment (96 % treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56 % higher MACE risk (hazard ratio 1.56; 95 % confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. Conclusions: Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.
    No preview · Article · Dec 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: Sore throat, cough, and hoarseness are the common and severe complications after general anesthesia with tracheal intubation. The efficacy of prophylactic administration of corticosteroids in reducing the incidence of postoperative complications is controversial. Thus, we conducted a meta-analysis to assess the effects of corticosteroids in the prevention of postoperative complications. Methods: A comprehensive literature search of Pubmed, Embase, and Web of Science was conducted to identify relative trials. Eligible studies were randomized controlled trials (RCTs) that assessed the effect of corticosteroids for preventing postoperative complications. The outcomes included the prevalence of postoperative sore throat, cough, hoarseness, laryngeal edema, and reintubation. A random-effects or fixed-effects model was used to pool the estimates, according to the heterogeneity among the included studies. Results: Eighteen RCTs with a total of 2685 patients were included in this meta-analysis. Pooled estimates showed that corticosteroids significantly reduced the incidence of postoperative sore throat, hoarseness, and cough. Moreover, corticosteroids had a positive effect on the incidence of laryngeal edema and reintubation. Subgroup analysis showed that corticosteroids significantly decreased the incidence of severe sore throat and hoarseness, but not cough. Conclusion: Evidence from this meta-analysis of 18 RCTs indicated that prophylactic administration of corticosteroids is not only effective in reducing the incidence and severity of postoperative sore throat and hoarseness, but also the incidence of laryngeal edema and reintubation.
    No preview · Article · Dec 2015 · Clinical Drug Investigation
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    ABSTRACT: Background Avibactam is a non-β-lactam β-lactamase inhibitor that restores the in vitro activity of β-lactams, such as ceftazidime, against bacterial pathogens harboring Ambler class A, C, and some class D β-lactamases. Objective This randomized, double-blind, placebo-controlled, phase I study (NCT01920399) evaluated the safety, tolerability, and pharmacokinetics of single and repeated doses of avibactam and ceftazidime in healthy Chinese subjects. Methods Sixteen healthy Chinese males aged 18–45 years were randomized 3:1 to receive 2000 mg ceftazidime and 500 mg avibactam (n = 12) or matched placebo (n = 4) as a 120-min intravenous infusion, once on Days 1 and 9, and every 8 h on Days 2–8. Results Avibactam and ceftazidime showed time-independent pharmacokinetics. Plasma exposure to avibactam and ceftazidime was similar following single and multiple dosing and accumulation of either agent was negligible. The majority of the avibactam and ceftazidime dose was recovered in urine. Adverse events were reported in three subjects (25.0 %) in the ceftazidime-avibactam group and one subject (25.0 %) in the placebo group. Two subjects in the ceftazidime-avibactam group had elevations in transaminases and one subject in the placebo group had elevated serum bilirubin levels that were considered causally related to study treatment. All adverse events were of mild intensity. Conclusions Single and multiple doses of 2000 mg ceftazidime and 500 mg avibactam were well tolerated in healthy Chinese subjects, and the observed pharmacokinetics were comparable to previous studies conducted in Western subjects.
    No preview · Article · Dec 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: Ramucirumab is a fully immunoglobulin G (lgG) monoclonal antibody targeting vascular endothelial growth factor receptor type 2 (VEGFR2). Previous clinical trials suggested ramucirumab could improve the survival and increase the risk of adverse effects. Here, we aimed to assess the efficacy and safety of ramucirumab in the treatment of advanced solid tumors. Methods: Publications were searched from Pubmed, Embase database and clinicaltrials.gov. Hazard ratio (HR) and 95 % confidence interval (95 % CI) were calculated to evaluate efficacy, and the risk ratio (RR) for adverse effects. Results: Ten relevant studies were included. Ramucirumab resulted in significant benefit in overall survival [OS, HR and 95 % CI 0.87 (0.82-0.93), I (2): 0.0 %] and progression-free survival [PFS, HR and 95 % CI 0.74 (0.66-0.82), I (2): 67.4 %]. Also the difference of time to progression (TTP) and objective response rate (ORR) between two groups were also significant [0.70 (0.57-0.88) and 1.78 (1.40-2.25), respectively]. Ramucirumab could increase the risk of total adverse effects (TAEs, of any grade) by 1 % (from 0 to 2 %) and severe adverse effects (SAEs, grade > 2) by 17 % (from 9 to 26 %). The most frequently occurring TAEs were fatigue (54.71 %), neutropenia (42.74 %), bleeding (37.55 %), nausea (34.63 %) and stomatitis (33.74 %). Most frequently occurring SAEs (grade ≥3) were neutropenia (33.43 %), fatigue (12.08 %), leukopenia (10.59 %), hypertension (8.99 %) and liver injury (8.74 %). Conclusion: Ramucirumab could improve OS and PFS for patients suffering from advanced solid tumors. Ramucirumab could increase the risk of TAEs and SAEs.
    No preview · Article · Nov 2015 · Clinical Drug Investigation
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    ABSTRACT: Background: Patients with chronic obstructive pulmonary disease (COPD) are at elevated risk of pneumococcal infection. A 13-valent pneumococcal conjugate vaccine (PCV13) was approved for protection against invasive disease and pneumonia caused by Streptococcus pneumoniae in adults. This study estimated the incremental cost-effectiveness ratio (ICER) of vaccinating COPD patients ≥50 years old with PCV13 compared with current vaccination policy (CVP) with 23-valent pneumococcal polysaccharide vaccine. Methods: A Markov model accounting for the risks and costs for all-cause non-bacteremic pneumonia (NBP) and invasive pneumococcal disease (IPD) was developed. All parameters, such as disease incidence and costs (€; 2015 values), were based on published data. The perspective of the analysis was that of the Spanish National Healthcare System, and the horizon of evaluation was lifetime in the base case. Vaccine effectiveness considered waning effect over time. Outcomes and costs were both discounted by 3 % annually. Results: Over a lifetime horizon and for a 629,747 COPD total population, PCV13 would prevent 2224 cases of inpatient NBP, 3134 cases of outpatient NBP, and 210 IPD extra cases in comparison with CVP. Additionally, 398 related deaths would be averted. The ICER was €1518 per quality-adjusted life-year (QALY) gained for PCV13 versus CVP. PCV13 was found to be cost effective versus CVP from a 5-year modelling horizon (1302 inpatient NBP and 1835 outpatient NBP cases together with 182 deaths would be prevented [ICER €25,573/QALY]). Univariate and probabilistic sensitivity analyses confirmed the robustness of the model. Conclusions: At the commonly accepted willingness-to-pay threshold of €30,000/QALY gained, PCV13 vaccination in COPD patients aged ≥50 years was a cost-effective strategy compared with CVP from 5 years to lifetime horizon in Spain.
    No preview · Article · Nov 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objective: Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI. Methods: Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 μg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0-6) after dosing (Study 2). Results: Study 1: differences, with corresponding 90 % confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated. Conclusion: The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.
    No preview · Article · Nov 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: A fixed-dose combination (FDC) of aspirin and clopidogrel bisulfate may improve medication adherence. However, the absence of data on the relative antiplatelet efficacy of FDC and separate dual pills (SDP) of aspirin and clopidogrel in real-world patients with stable coronary artery disease is a major factor retarding clinical introduction of such an FDC. Methods: This was a single-centre, randomized, open-label, parallel-group, non-inferiority trial. Patients who maintained a regimen of separate aspirin and clopidogrel pills for at least 1 year after drug-eluting stent implantation without adverse events were enrolled. Patients were randomly assigned to either the FDC group or the SDP group. Antiplatelet efficacy and tolerability were assessed at baseline and at 4 weeks. Results: Of the 93 enrolled patients, 83 (FDC group: n = 42; SDP group: n = 41) completed the study. The difference in the changes in P2Y12 percentage inhibition did not exceed the predetermined value for inferiority [mean difference -1.7; 95 % confidence interval (CI) -6.9 to 4.5, p < 0.001 for non-inferiority]. The changes from baseline to 4 weeks in P2Y12 reaction units (PRU) (mean difference 9.7 PRU, p = 0.46), maximal platelet aggregation (mean difference 2.0 %, p = 0.44) and aspirin reaction units (ARU) (mean difference -2.3 ARU, p = 0.88) did not differ significantly between the treatment groups. The tolerability of the FDC formulation was similar to that of SDP therapy (p = 0.68). Conclusion: In patients with prior percutaneous coronary intervention, the antiplatelet efficacy of the aspirin/clopidogrel FDC was non-inferior to that of SDP and the tolerability of the two regimens was similar after 4 weeks of treatment.
    No preview · Article · Oct 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objective: Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy. Methods: A prospective study in patients with primary, cryptogenic or symptomatic epilepsy, who were taking branded levetiracetam and were switched to generic levetiracetam. Patients were consecutively recruited from January 2013 to January 2015. We evaluated efficacy, tolerability and compliance before switching (T0) and after 6 months of therapy (T1). Evaluations were scheduled as follows: baseline, 7 and 15 days, 1, 3 and 6 months. At each visit clinical diary seizures, physical and neurological examination, laboratory parameters and electroencephalogram were evaluated. Results: Fifty-nine patients, equally mixed by sex, were included in the study. Mean age was 26.1 years. Forty-seven per cent of the patients enrolled received levetiracetam as monotherapy. One patient was lost during the follow-up: so at T1 we had 58 patients (28 monotherapy and 30 polytherapy). At T0 and at T1, there was no statistically significant difference in terms of seizure frequency and intensity, occurrence of adverse events, laboratory parameters and electroencephalographic features. Two patients stopped treatment with the generic (both at 3 months after the switch) and restarted therapy with brand levetiracetam because of seizure increase. At the end of the study, the switchback rate was 3.4 %. Conclusions: No increase of seizures and adverse effects were observed when branded levetiracetam was interchanged to a generic equivalent. More studies should be conducted with a larger series of patients to confirm these results.
    No preview · Article · Oct 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: Oxidative stress in drug-induced thrombocytopenia (TP) has been discussed. This study was carried out to assess the oxidative stress in patients with normal platelet count (NPC) and TP after linezolid (LZD) treatment and to evaluate if TP caused by LZD is associated with a reduction in antioxidation ability and an increase in lipid peroxidative product in platelets. Methods: After LZD treatment for 20 days, 44 patients with TP and 73 patients with NPC were included in this study. Blood samples were collected on the day before medicine treatment and day 7, 14, and 20 after LZD therapy. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cholesterol as well as the activities of antioxidative enzyme were estimated. In addition, we identified 37 patients with TP caused by low-dose methotrexate (7.5-25 mg/week) therapy as a positive control group. Results: In total, 37.60 % of cases presented with TP on the 20th day of LZD administration. Individuals with TP had significantly elevated levels of ROS and MDA, low levels of superoxide dismutase (SOD) and catalase (CAT), significantly decreased high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol levels, and increased oxidized-LDL levels in comparison to individuals with NPC. However, no significant changes in the levels of glutathione-peroxidase were found in the course of time. In all cases with LZD, significant increases in levels of ROS, MDA, and ox-LDL were found in the 20-day samples compared with their respective samples before LZD treatment. Correlation analysis revealed a positive association between platelet count and levels of SOD on day 20 and CAT on days 14 and 20 in plasma, a negative association between platelet count and level of MDA and ROS on days 14 and 20 in patients with LZD-induced TP. Conclusions: The oxidative stress markers were increased in LZD-induced TP, suggesting that oxidative damage might be the underlying mechanism.
    No preview · Article · Oct 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objective: Breakthrough pain (BTP) is highly prevalent in patients with cancer and is strongly associated with adverse outcomes related to health status, mood, anxiety and depression. However, studies on the effect of BTP medication on quality of life (QOL) are lacking. The purpose of this study was to provide a qualitative evaluation of the effect of sublingual fentanyl tablets (SFT), a therapy specifically developed for BTP, on the QOL of cancer pain patients. Methods: We conducted a multicentre, prospective observation post-authorisation, open-label study between March and December 2013. The study consisted of a screening visit and four assessment points at 3, 7, 15 and 30 days. Pain intensity (PI), frequency of BTP, onset of pain relief and adverse events (AEs) were assessed at each visit. Anxiety and depression were evaluated using the validated Hospital Anxiety and Depression Scale (HADS) and health status using the Short Form 12, version 2 (SF-12v2) Health Survey. Results: Of the 102 patients considered eligible, 81 (79.4 %) were enrolled; of these, 69 (85.1 %) completed the study. Significant pain reduction was achieved for average PI (p < 0.001) compared with baseline. At the end of the observational period, HADS scores showed significant improvement in the depression subscale (p = 0.005) and the anxiety subscale (p < 0.001). Similarly, SF-12 scores showed significant improvement, both in the mental component score (p < 0.001) and the physical component score (p = 0.002). SFT was well-tolerated and only one patient withdrew from the study due to drug-related AEs. Conclusion: SFT represents an effective, well-tolerated treatment for cancer BTP. Results provide consistent evidence for the positive impact of SFT on health-related QOL and physical functioning as well as other co-morbidities of cancer BTP such as anxiety and depression.
    No preview · Article · Oct 2015 · Clinical Drug Investigation
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    ABSTRACT: Oral teneligliptin [Teneglucon(®) (Argentina)], a dipeptidyl peptidase-4 inhibitor, is indicated for the treatment of adults with type 2 diabetes (T2DM). This article reviews the pharmacology, therapeutic efficacy and tolerability of teneligliptin in the treatment of adults with T2DM. In 12- or 16-week, placebo-controlled phase 2 and 3 trials, oral teneligliptin 20 or 40 mg once daily, as monotherapy or in combination with metformin, glimepiride or pioglitazone improved glycaemic control, including in patients with end-stage renal disease, and was generally well tolerated. Most treatment-emergent adverse events were of mild intensity and relatively few patients discontinued treatment because of these events. Improvements in glycaemic control observed in short-term trials were maintained at 52 weeks in extension phases of these trials and in 52-week interventional studies, with no new safety concerns identified during this period. In the absence of direct head-to-head clinical trials, the position of teneligliptin relative to other antidiabetic agents in the management of T2DM remains to be determined. In the meantime, teneligliptin is a useful treatment option for adults with T2DM who have not responded adequately to diet and exercise regimens, or the addition of antidiabetic drugs.
    No preview · Article · Oct 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: We studied the effect of achieving sustained virological response (SVR) on the risk of developing hepatocellular carcinoma (HCC) in patients with hepatitis C receiving anti-hepatitis C virus treatment. Avoiding HCC is considered the main long-term benefit of successful antiviral treatment. Methods: Our literature search extended up to June 2015. We identified all studies that assessed the risk of HCC in patients achieving or not achieving SVR. Meta-analysis was based on a standard random-effect model. The end-point was occurrence of HCC compared between patients with and without SVR; this end-point was expressed as an odds ratio and percent reduction in risk and was also presented separately for patients with and without cirrhosis. All results estimates presented with 95 % confidence intervals (CIs). The presence of any temporal trend in these indexes was investigated by standard meta-regression. Results: Our search identified 25 observational studies (19,822 patients). The odds ratio of HCC for SVR versus no-SVR was 0.19 (95 % CI 0.15-0.24) in the overall series of 25 studies. The difference in this index between patients with any stage of fibrosis/cirrhosis and those with cirrhosis was small. With regard to risk difference, the 25 studies indicated an overall reduction of 10 % (95 % CI 8.00-12.0); this effect was much less pronounced in the group with any stage of fibrosis/cirrhosis (risk difference 6.7 %) than in the selected group with cirrhosis (risk difference 22 %). Meta-regression showed no temporal trend. Conclusion: Our analysis was successful in providing an updated overview on this controversial topic. Some pharmacoeconomic assessments are also presented to interpret the clinical results of our analysis.
    No preview · Article · Oct 2015 · Clinical Drug Investigation
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    ABSTRACT: Background and objectives: Desloratadine, the major active metabolite of loratadine, is a non-sedating long-acting antihistamine that is widely used in the treatment of allergic rhinitis and chronic idiopathic urticaria. This study aimed to investigate the prevalence of desloratadine slow-metabolizer (DSM) phenotype and the effects of food on the pharmacokinetics of desloratadine and its active metabolite 3-OH-desloratadine in healthy Chinese volunteers. Methods: A total of 46 healthy Chinese male volunteers were included in this investigation. All subjects received a single dose of a 5-mg desloratadine tablet under fasting or fed conditions and the plasma concentrations of desloratadine and 3-OH-desloratadine were measured by liquid chromatography-tandem mass spectrometry. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. The individuals with a 3-OH-desloratadine-to-desloratadine exposure ratio lower than 10 % or a desloratadine half-life (t 1/2) of ≥50 h were supposed to be DSM. Results: There was only one DSM among the 46 volunteers, with a prevalence of 2.2 %. Moreover, administration in a fed state resulted in 34.07 and 32.06 % decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity for desloratadine and 47.26 and 48.46 % for 3-OH-desloratadine compared with those values under fasting conditions. Conclusions: Taken together, these results indicated that the incidence of the DSM phenotype in the Chinese population was low and that food intake could significantly decrease the absorption rate and extent of desloratadine.
    No preview · Article · Oct 2015 · Clinical Drug Investigation