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

2015 Impact Factor Available summer 2016
2014 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

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

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  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    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.
    Clinical Drug Investigation 10/2015; DOI:10.1007/s40261-015-0343-1
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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.
    Clinical Drug Investigation 10/2015; DOI:10.1007/s40261-015-0338-y
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    ABSTRACT: Background: Sorafenib might prevent hepatocellular carcinoma (HCC) recurrence caused by the promotion of neoangiogenesis after transarterial chemoembolization (TACE). Objectives: To evaluate the efficacy and safety of TACE followed by sorafenib for treating advanced HCC. Patients and methods: We retrospectively analyzed 95 advanced HCC patients treated with TACE between July 2008 and December 2012 at our institution. Twenty-four patients received TACE followed by sorafenib within 14 days (S-TACE) and 71 received TACE alone. Progression-free survival (PFS) and cumulative survival from the time of non-responsiveness to TACE were compared between groups and predictive factors for PFS were analyzed. Results: The median patient age was 72.2 years and 74 patients were male (77.9 %). Although median tumor size was similar between groups, the mean tumor number was significantly higher in the S-TACE versus TACE-alone group (16 vs. 8, P = 0.04). The number of prior treatments was significantly higher in the S-TACE group. Other baseline variables were similar. There were two severe adverse events in the S-TACE group and none in the TACE-alone group. Median PFS (189 vs. 106 days, P = 0.02) and median overall survival time (861 vs. 467 days, P = 0.01) from the time of non-responsiveness to TACE were significantly longer with S-TACE than TACE alone. Adjusting for significant factors in univariate analysis, multivariate analysis indicated that sorafenib administration, tumor size, and alanine transaminase were independent predictors of PFS. Conclusion: TACE followed by sorafenib significantly improved PFS and survival in patients with advanced HCC unresponsive to TACE.
    Clinical Drug Investigation 10/2015; DOI:10.1007/s40261-015-0333-3
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    ABSTRACT: Intra-articular administration of hyaluronic acid is a valuable therapeutic tool for the management of patients with osteoarthritis. However, in recent years numerous formulations containing hyaluronic acid administrable by oral route have entered the market. Even if there are some data in the literature that have shown their effectiveness, systemic administration may expose a greater risk in certain situations. In fact, although hyaluronic acid is not considered a drug it is certain that it can interact with specific receptors and promote cell proliferation. This interaction may be potentially hazardous in cancer patients for which these oral formulations should be contraindicated.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0339-x
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    ABSTRACT: Background and objective: Long-term adverse effects of oral glucocorticoids are frequent and serious. Large between-patient variability in the pharmacokinetics of prednisolone might explain why drug dose is a poor predictor of drug-related toxicity. The aim of the study was to investigate relationships between prednisolone exposure and adverse effects. Methods: Male kidney transplant recipients were recruited for serial blood sampling and assessment of glucocorticoid-related adverse effects including dyslipidaemia, abnormal body fat distribution, Cushingoid appearance and impaired quality of life. Total and free prednisolone plasma concentrations were determined using ultra-high-performance liquid chromatography with tandem mass spectrometric detection. Prednisolone exposure was estimated using a limited sampling strategy. Results: Fifty-six patients were recruited. Patients had a mean age of 54 years and median time post-transplantation of 75 months. Median prednisolone dose was 5 mg. Mean area under the plasma concentration-time curve was 2390 nmol h/L (±580) (SD) and 175 nmol h/L (±78) for total and free prednisolone, respectively. Waist to upper arm circumference ratio was positively associated with free prednisolone plasma exposure with a Spearman correlation coefficient of 0.30 (p value 0.02). The correlation coefficient was 0.24 (p value 0.08) for neck to upper arm circumference ratio and free prednisolone plasma exposure. The clinical Cushingoid phenotype as determined by the Visual Assessment of Cushing's Severity (VACS) score was associated with a reduced score relating to physical functioning on the SF-12, but there was no significant relationship between free prednisolone plasma exposure and quality-of-life scores. Lipid levels and haemoglobin A1c (HbA1c) were not associated with total or free prednisolone exposure. Conclusions: There is a positive correlation between free prednisolone plasma exposure and waist to upper arm circumference ratio in adult male kidney transplant recipients on low maintenance prednisolone doses. There is no significant association between total or free prednisolone plasma exposure and plasma glucose and lipid levels in the low prednisolone dose range.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0334-2
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    ABSTRACT: Background and objective: Patients with bipolar I disorder and schizophrenia have an increased risk of obstructive sleep apnea. The effects of armodafinil, a weak cytochrome P450 (CYP) 3A4 inducer, on pharmacokinetics and safety of risperidone, an atypical antipsychotic used to treat major psychiatric illness, were investigated. Methods: Healthy subjects received 2 mg risperidone alone and after armodafinil pretreatment (titrated to 250 mg/day). Pharmacokinetic parameters were derived from plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone (formed via CYP2D6 and CYP3A4), collected before and over 4 days after risperidone administration, and from steady-state plasma concentrations of armodafinil and its circulating metabolites, R-modafinil acid and modafinil sulfone. Safety and tolerability were assessed. Results: Thirty-six subjects receiving study drug were evaluable for safety; 34 were evaluable for pharmacokinetics. Risperidone maximum plasma concentration (C max) decreased from mean 16.5 ng/mL when given alone to 9.2 ng/mL after armodafinil pretreatment (geometric mean ratio [90 % CI] 0.55 [0.50-0.61]); area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) decreased from 92.3 to 44.5 ng·h/mL (geometric mean ratio [90 % CI] 0.51 [0.46-0.55]). C max and AUC0-∞ for 9-hydroxyrisperidone were also reduced (geometric mean ratios [90 % CI] 0.81 [0.77-0.85] and 0.73 [0.69-0.77], respectively). Adverse events were consistent with known safety profiles. Conclusion: Consistent with CYP3A4 induction, risperidone and 9-hydroxyrisperidone systemic exposure was reduced in the presence of armodafinil. Concomitant armodafinil and risperidone use may necessitate risperidone dosage adjustment, particularly when starting or stopping coadministration of the two drugs. However, any such decision should be based on patient disease state and clinical status.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0330-6
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    ABSTRACT: Objectives: The aim of this work was to investigate the efficacy and safety of loading-dose rosuvastatin therapy in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing elective percutaneous coronary intervention (PCI). Methods: A total of 126 patients (≥70 years old) with NSTEACS were randomly divided into two groups: (1) loading-dose rosuvastatin-treated group, treated with rosuvastatin 20 mg 12 h prior to PCI, with a second dose administered just before PCI (n = 62), and (2) control-treated group, treated with the standard method according to ACC/AHA guidelines in UAP/NSTEMI 2007 (n = 64). All patients were required to take rosuvastatin 10 mg once a day starting 24 h after the surgery irrespective of the initial randomization assignment. The serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLox-1), high-sensitivity C-reactive protein (hs-CRP), creatinine kinase (CK)-MB, cardiac troponin I (cTnI), and brain natriuretic peptide (BNP) levels were measured prior to PCI and at 24 h and 30 days after PCI in both groups. The left ventricular ejection fraction (LVEF) levels were recorded prior to PCI and 30 days after PCI in both groups. Results: Compared to pre-PCI, the serum sLox-1, hs-CRP, CK-MB, and cTnI levels were increased at 24 h after PCI (all p < 0.05) in both groups. However, the increased sLox-1, hs-CRP, CK-MB, and cTnI values were significantly lower in the loading-dose rosuvastatin-treated group than in the control-treated group (p < 0.05). In addition the serum sLox-1 and hs-CRP levels were lower in the loading-dose rosuvastatin-treated group than in the control-treated group at 30 days after PCI. However, the decreased values of sLox-1and hs-CRP from 24 h after PCI to 30 days after PCI did not show any significant difference between the two groups. No significant difference was found in the serum ALT and Scr levels between the two groups before and after PCI. Compared to the control-treated group, the serum BNP level decreased (p < 0.05) and LVEF (p < 0.05) increased in the loading-dose rosuvastatin-treated group at 30 days after PCI. Conclusion: The loading-dose rosuvastatin therapy in elderly patients with non-ST-segment elevation acute coronary syndromes undergoing elective PCI can attenuate the increase in serum hs-CRP, sLox-1, CK-MB, and cTnI levels, reduce myocardial injury and inflammatory reaction caused by PCI, and improve the LVEF level at 30 days after PCI, ensuring an effective and safe therapy.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0335-1
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    ABSTRACT: Background and objective: As a β-adrenoceptor antagonist (β-blocker), esmolol can reduce cardiac output and the phosphodiesterase III inhibitor milrinone has been shown to improve heart contractility in patients with septic shock. This study was performed to assess the effects of esmolol combined with milrinone in patients with severe sepsis. Methods: This prospective randomized study was conducted in patients with severe sepsis in the intensive care unit of the Jiangxi Provincial People's Hospital (Nanchang, Jiangsu, China) between June 2013 and June 2014. Patients were randomly divided into control (C), milrinone (M), and milrinone-esmolol (ME) groups. The primary outcome was the rate of controlling the heart rate (HR) to achieve target levels. Secondary outcomes included the 28-day survival rate and changes in hemodynamic variables, organ function variables, myocardial injury markers, and the serum levels of proinflammatory factors. Result: A total of 90 patients with severe sepsis were included in this study (30 per group). The HR in the ME group was lower than in the M and C groups after 12 h. The rate of successful HR control during the first 96 h was significantly higher in the ME group (60.0 vs. 33.3 % in the M group, vs. 26.7 % in the C group). Also, patients in the ME group had higher 28-day overall survival compared with the M (Log rank statistic = 5.452; P = 0.020) and C groups (Log rank statistic = 10.206; P = 0.001). Additionally, several variables showed significant improvement in the ME group 96 h after treatment compared with the M and C groups (P < 0.05). Conclusion: Combination therapy with milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0325-3
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    ABSTRACT: Aim: This study aimed to describe the prescription pattern of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in an Italian setting, focusing on therapy duration, switching and adherence. Method: Historic cohort study, based on administrative databases of three Italian local health-units, was conducted. Patients with a prescription of antidepressants (ADs) in 2009 were enrolled and grouped into: (1) naïve, (2) already in treatment with the same drug and (3) already in treatment with a different drug. Therapy duration, switching and adherence [as medication possession ratio-(MPR)] were evaluated. A logistic regression model was performed to identify predictors of adherence. Results: There were 88,755 subjects recruited: 37 % naïve, 58 % already in treatment with the same drug and 4 % with different drug. A treatment duration of ≤3 months was found in 41 % of naïve patients, whereas the majority of patients already in treatment had a duration of ≥6 months. Switches occurred in 0.7 % of the whole cohort and mostly occurred between two different SSRIs. The 63 % of naïve patients had a low adherence (MPR < 60 %), whereas a good adherence (MPR ≥ 80 %) was found in 58 % of patients already in treatment with the same drug and in 39 % of those already in treatment with different drug. Predictors of adherence were: female gender, increasing comorbidity and pain absence. All ADs, except for fluoxetine and venlafaxine, showed a better adherence than paroxetine. Conclusion: Notwithstanding the difficulty to associate the AD prescription to the specific diagnosis of depression, this study highlighted a short duration and a low adherence of AD therapies, especially at the initiation of treatment. Physicians should carefully balance the need to prescribe these drugs, considering the great likelihood of a short duration of treatment and a very low level of adherence.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0332-4
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    ABSTRACT: The clinical utilization of psychotropic medications in pregnant women represents a significant challenge. Indeed, the risks of untreated severe mental disorders, particularly when complicated by substance-related and addictive disorders, must be carefully balanced against the potential teratogenic risks of pharmacological treatment. In this case, an alcohol addict, diagnosed with borderline personality disorder was treated successfully with several classes of psychotropic agents during the first trimester. In September 2014, while taking trazodone, lorazepam, quetiapine, mirtazapine, and flurazepam, this patient became aware that she was pregnant. After a perinatal psychiatrist consultation requested four months later, trazodone and flurazepam were progressively suspended and daily doses of lorazepam and quetiapine were lowered gradually. Mirtazapine dose remained unchanged. Apart from a mild gastro-esophageal reflux disease, birth outcome was normal.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0337-z
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    ABSTRACT: Background and objectives: A new biosimilar human recombinant epoetin alfa product (PDA10) has been developed by PanGen Biotech Inc., Korea. This study was planned to demonstrate the pharmacokinetic and pharmacodynamic comparability of PDA10 to an existing epoetin alfa (Eprex) after a single intravenous administration to healthy adult male volunteers. Methods: A randomized, double-blinded, single-dose, crossover study was conducted in 30 subjects. The subjects were assigned randomly to one of two sequence groups, and single doses of 100 IU/kg PDA10 or Eprex were administered intravenously on each of 2 treatment days separated by a 4-week washout period. Plasma erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay and the pharmacokinetic parameters of the two treatments were compared. The time course and area under the effect curve (AUEC) of absolute reticulocyte counts were used as surrogate parameters for the pharmacodynamic evaluation. Adverse events (AEs) were recorded. Results: A total of 30 subjects were enrolled, and 27 completed the study. The geometric mean ratios (PDA10/Eprex) of erythropoietin for maximum plasma concentration (C max) and area under the plasma concentration-time curve to the last measurable concentration (AUC0-last) after intravenous administration of 100 IU/kg were 1.00 (90 % confidence interval [CI] 0.96-1.05) and 0.96 (90 % CI 0.93-1.00). The absolute reticulocyte counts of PDA10 and Eprex were similar, as determined from the maximum reticulocyte count and AUEC0-last values. Treatment-emergent AEs were mild and occurred in seven subjects. Conclusion: PDA10 and Eprex met the regulatory criteria for bioequivalence with respect to their pharmacokinetic profiles and pharmacodynamic actions.
    Clinical Drug Investigation 09/2015; 35(10). DOI:10.1007/s40261-015-0327-1
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    ABSTRACT: Background and objective: Chronic gastritis frequently progresses into precancerous intestinal metaplasia and intraepithelial neoplasia lesions. Rebamipide is a free radical scavenger and we assessed its efficacy on clinical symptoms, gastric mucosal lesions, pathologic grade, and immunohistochemistry in chronic gastritis patients. Methods: 178 eligible patients were randomized into treatment and control groups. Both groups followed an optimized lifestyle for 26 weeks, but the treatment group was additionally medicated with rebamipide 0.1 g three times per day. Upper gastrointestinal endoscopy was performed in all patients to evaluate the severity of gastritis by the Modified Lanza Scoring (MLS) and histological changes were evaluated by the Updated Sydney System Score (USSS). Gastric mucosa immunohistochemistry in the treatment group was performed using the intestinal metaplasia markers caudal type homeobox transcription factor 2 (CDX2) and trefoil factor 3 (TFF3) detection. Results: There were significant outcome differences between the treatment and control groups regarding the clinical symptom scores (2.62 ± 1.86 vs. 1.55 ± 1.61, P = 0.0001), gastric mucosal lesion scores (0.57 ± 1.05 vs. 0.16 ± 0.90, P = 0.002), and inflammation (P < 0.05). Only in the treated patients were the rates of intestinal metaplasia (P = 0.017 vs. P = 0.123) and low-grade intraepithelial neoplasia (P = 0.005 vs. P = 0.226) significantly reduced after 26 weeks. The percentages of CDX2 (31.5 vs. 15.7 %, P = 0.021) and TFF3 (44.9 vs. 25.8 %, P = 0.012) expressing gastric mucosa cells were significantly lower after rebamipide medication than pre-treatment values. Conclusions: Rebamipide improved the clinical symptoms, gastric mucosal lesions, and pathological grades of chronic gastritis patients and decreased the expression rates of CDX2 and TFF3 in gastric cells.
    Clinical Drug Investigation 09/2015; 35(10). DOI:10.1007/s40261-015-0329-z
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    ABSTRACT: Background: Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA(®) Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. Objective: Assess effects of alcohol on hydrocodone ER pharmacokinetics. Study design: Open-label, crossover (January 25-April 30, 2010). Setting: Single center. Participants: Forty healthy adults. Intervention: Subjects received all four treatments in a randomized manner (separated by a minimum 5-day washout): hydrocodone ER 15 mg with 240 mL water and 240 mL orange juice containing 4, 20, and 40 % alcohol in a fasted state. Naltrexone was administered to minimize opioid-related adverse events. Main outcome measure: Effect of alcohol on pharmacokinetics of hydrocodone ER assessed by comparing systemic exposure [maximum plasma drug concentration (C max) and area under the plasma drug concentration-versus-time curve from time 0 to infinity (AUC0-∞)] after administration with alcohol or with water. Results: Geometric means ratios of hydrocodone ER with 4, 20, and 40 % alcohol relative to water were 1.05, 1.09, and 1.14, respectively, for C max and 1.07, 1.13, and 1.17, respectively, for AUC0-∞. All 90 % confidence intervals for these geometric means ratios fell within the limits of 0.8 and 1.25. Increasing alcohol concentrations did not notably affect systemic exposure but were associated with increased adverse events. Conclusions: Hydrocodone ER tablets were resistant to dose dumping when administered with alcohol in healthy subjects based on similar systemic exposures observed across all treatments.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0324-4
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    ABSTRACT: Background and objective: No sufficient research has focused on the relationship between meloxicam use and acute pancreatitis. This study aimed to explore this issue in Taiwan. Methods: This case-control study was conducted using the database of the Taiwan National Health Insurance Program. In all, there were 6780 cases aged 20-84 years who were newly diagnosed with acute pancreatitis during the period 1998-2011, and 21,393 control subjects without acute pancreatitis. Cases and controls were matched for sex, age and comorbidities. Odds ratios (ORs) and 95 % confidence intervals (CIs) were measured to explore the associations between acute pancreatitis, meloxicam use and comorbidities, using a multivariable unconditional logistic regression model. Results: After controlling for potential confounding factors, the adjusted OR for acute pancreatitis was 1.76 (95 % CI 1.30-2.40) for subjects with current use of meloxicam, in comparison with subjects who had never used meloxicam. The adjusted OR decreased to 1.29 (95 % CI 0.82-2.03) for subjects with late use of meloxicam, but without statistical significance. Conclusions: Current use of meloxicam is associated with increased odds of acute pancreatitis. Clinicians should consider the potential risk of acute pancreatitis when prescribing meloxicam.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0326-2
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    ABSTRACT: Background and objectives: Acute otitis media (AOM) not only affects childhood quality of life (QoL), but can also affect parental QoL. We adapted a previously published questionnaire on the effect of childhood recurrent ear, nose and throat infections on parental QoL for use with AOM and used it in an observational, multicentre, prospective study of children with AOM. Methods: The AOM-specific parental QoL questionnaire grouped 15 items into emotional, daily disturbance, total and overall parental QoL impact scores. The questionnaire was assessed using item-convergent and item-discriminant validity criteria and internal consistency reliability; and then used with parents of children aged <6 years diagnosed with AOM at 73 practices in Germany, Italy, Spain, Sweden and the UK. Bivariate analyses explored the differences in mean parental QoL impact scores by various characteristics. Results: The questionnaire demonstrated good to excellent internal consistency reliability for the various components (Cronbach's α 0.82-0.97). There were 1419 AOM episodes among 5882 healthy children over 1 year, of which 1063 episodes (74.9 %) among 852 children had a questionnaire. Parents reported interrupted sleep (68.4 %), worry (51.0 %), altered daily schedule (44.6 %) and less leisure time (41.5 %) with a score ≥3 (1 = least to 5 = most impact). Factors that adversely affected parental QoL included: increased parental perception of AOM severity, younger child age and multiple AOM episodes. Conclusions: The AOM-specific parental QoL questionnaire demonstrated good performance across five European countries. Parental QoL was affected by childhood AOM proportionally to severity, number of episodes and younger child age.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0319-1
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    ABSTRACT: Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation. A single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (C max), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUC t ) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90 % confidence intervals. The pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the C max, AUC t and AUC∞ values fell within the 80-125 % acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78 %) and ibuprofen (96.45 %) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination. Concomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of either drug. The IV and oral dose forms of such a combination are pharmacokinetically equivalent.
    Clinical Drug Investigation 09/2015; DOI:10.1007/s40261-015-0320-8