International journal of clinical pharmacology and therapeutics (INT J CLIN PHARM TH )

Description

The International Journal of Clinical Pharmacology and Therapeutics appears monthly and publishes manuscripts containing original material with emphasis on the following topics: Clinical trials, Pharmacoepidemiology - Pharmacovigilance, Pharmacodynamics, Drug disposition and Pharmacokinetics, Quality assurance, Pharmacogenetics, Biotechnological drugs such as cytokines and recombinant antibiotics. Case reports on adverse reactions are also of interest.

  • Impact factor
    1.20
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    Impact factor
  • 5-year impact
    1.36
  • Cited half-life
    8.10
  • Immediacy index
    0.33
  • Eigenfactor
    0.00
  • Article influence
    0.35
  • Website
    International Journal of Clinical Pharmacology & Therapeutics website
  • Other titles
    International journal of clinical pharmacology and therapeutics, Clinical pharmacology and therapeutics
  • ISSN
    0946-1965
  • OCLC
    29934177
  • Material type
    Periodical
  • Document type
    Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of this study was to evaluate the incidence and type of adverse drug reactions (ADRs) and identify risk factors for ADRs in elderly patients within 30 days following discharge from an internal medicine clinic. Methods: A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between September 1st and November 30th 2012. Patients aged ≥ 65 years discharged from the clinic during the study period were eligible for inclusion in the study. The follow-up visit was scheduled ~ 30 days after discharge. During the visit, the patients were assessed for the occurrence of ADRs. Two independent physicians evaluated each possible ADR by using the Naranjo ADR probability scale. Multivariate logistic regression analysis was used to identify predisposing factors for ADRs. Results: There were 209 patients included in this study. A total of 72 ADRs were detected in 63 (30.1%) patients. The most frequent ADRs were bleeding disorders associated with warfarin therapy, followed by hypoglycemia associated with antidiabetics. Five (6.9%) ADRs, which resulted in hospital admission, were classified as serious. Multivariate logistic regression analysis indicated number of prescribed drugs ≥ 4 and prescription of furosemide and warfarin to be associated with increased risk of ADRs. Conclusions: Our study showed that ADRs are an important cause of morbidity in elderly patients after hospital discharge. Judicious prescription of drugs and careful and frequent monitoring of drug therapy are necessary to reduce the risk of ADRs.
    International journal of clinical pharmacology and therapeutics 07/2014;
  • Alexandra Werner-Busse, Karel Kostev, Guido Heine, Margitta Worm
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    ABSTRACT: Background and aim: Atopic dermatitis is often associated with atopic comorbidities such as allergic rhinitis, allergic asthma and food allergy. The aim of the present study was to analyze treatment data pertaining to atopic dermatitis patients in Germany with regard to the presence of other atopic comorbidities in the primary care and to investigate whether the presence of atopic codiagnoses has an impact on the treatment of atopic dermatitis (AD) patients. Methods: We used data from the Disease Analyzer database (IMS HEALTH, Germany) including 1,631 physicians (general practitioners, dermatologists and pediatricians) and 3.3 million patients. 39,642 (7.5%) of these patients were treated by dermatologists, 17,124 (5.2%) by pediatricians and 15,774 (0.9%) by general practitioners and had a documented diagnosis of atopic dermatitis. Results: 46.4% of AD patients treated by general practitioners, 42.5% by dermatologists and 32.0% by pediatricians were codiagnosed with one defined atopic diseases (allergic asthma, urticaria, allergic rhinitis and food allergy). In patients without AD, the proportion of atopic diseases was significantly smaller (41.4% for those treated by general practitioners, 38.4% for those treated by dermatologists, 26.4% for those treated by pediatricians). AD patients with another atopic comorbidity received topical corticosteroids (CS) (42.5%) more frequently than those without comorbidity (46.4% vs. 41.4% for patients treated by general practitioners, 42.5% vs. 38.4% for patients treated by dermatologists, 32.0% vs. 26.4% for patients treated by pediatricians). The general practitioners and pediatricians prescribed systemic corticosteroids to 13.2% and 7.8% of AD patients with additional atopic diseases, while the rate was only 5.1% and 3.0% in patients without comorbidities. Conclusion: In AD patients, the share of patients diagnosed with atopic diseases is significantly higher than in patients without AD. AD outpatients with concomitant atopic comorbidities receive topical, but also systemic corticosteroid prescriptions more frequently.
    International journal of clinical pharmacology and therapeutics 07/2014;
  • Stefan Roepcke, Ruediger Nave, Jane Cyran, Nele Plock, Gezim Lahu, Axel Facius
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    ABSTRACT: Objective: Teduglutide is a recombinant analogue of human glucagonlike peptide-2 (GLP-2) that was recently approved by the US and European regulatory agencies FDA and EMA for the treatment of short bowel syndrome (SBS). The objectives of this work were, firstly, to develop a population pharmacokinetic (popPK) model based on the available PK data of the entire clinical development program and, secondly, to utilize the model for the justification of the proposed dosing regimen. The exploratory analysis was based on a previously established structural PK model and focused primarily on the investigation of covariate effects. Results: The plasma concentrationtime profiles of teduglutide after subcutaneous application were adequately described by a 1-compartment model with first order absorption and elimination. The area under the curve (AUC) was lower for male subjects, for subjects with higher creatinine clearance, for overweight subjects, and for SBS patients. However, except for subjects with severe renal impairment no clinically relevant effects on AUC were identified. Conclusion: Our model-based analysis supports the approved dose adjustment for SBS patients with and without renal impairments maintaining the exposure in a value range with acceptable variance for the target population.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Despite the variety of therapeutic options for the management of type 2 diabetes mellitus, many patients fail to meet glycated hemoglobin (HbA1c) targets. The relative contribution of postprandial plasma glucose (PPG) to overall HbA1c is estimated at 40 - 60%, with the effect of PPG on HbA1c being prominent in patients on basal insulin.The development of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been an important achievement in diabetes management and has become an established treatment. Of available GLP-1RAs, lixisenatide is a once-daily prandial GLP-1RA that has been shown to produce a reduction in HbA1c with a pronounced postprandial effect, suggesting a complementary effect between lixisenatide and basal insulin on PPG and fasting plasma glucose, resulting in a beneficial effect on body weight in all populations. Therefore, lixisenatide will make an important addition to current options for treating diabetes, especially for patients not achieving glycemic targets with basal insulin therapy.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Objective: A starting dose in first-in-human (FIH) studies has been determined carefully to guarantee the safety of participants in the study but sometimes it seems to be too conservative. The objective of the present study is to investigate a reasonable safety factor to enable effective drug development without serious safety problems in study participants. Methods: No-observedadverse- effect levels (NOAELs) in nonclinical studies, starting doses in FIH studies, and approved doses in Japan were reviewed by documents disclosed by health authorities, and the relationships among each parameter were analyzed retrospectively. Results: The present study suggested that the starting doses in the past FIH studies had been determined very prudently, and revealed that there were significant differences between the starting dose and approved dose. Conclusion: It would be possible to develop new drugs effectively without serious safety risks if a reasonable safety factor had been applied to determine a starting dose in FIH studies.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: The aim of this study was to compare pharmacokinetic characteristics of fixed-dose combination (FDC) of two different salt form of amlodipine, amlodipine adipate/valsartan and amlodipine besylate/ valsartan, in healthy Korean volunteers under fasting conditions. A randomized, open-label, single-dose, two-treatment, two-way crossover study with a 14-day wash-out period was conducted. Plasma samples were collected for up to 144 hours for amlodipine and 24 hours for valsartan. Plasma concentrations of amlodipine and valsartan were analyzed using a validated ultra-performance liquid chromatography tandem mass-spectrometry. A non-compartmental method was used to calculate pharmacokinetic parameters. Vital signs and adverse events were monitored and physical examinations, laboratory tests, and electrocardiograms were conducted to evaluate safety. 44 subjects completed the study. The 90% CIs for the geometric mean ratio of Cmax and the AUC0-t were 93.5 - 100.4% and 93.2 - 98.3% for amlodipine, and 92.1 - 121.3% and 94.1 - 115.2% for valsartan, respectively. 17 adverse events occurred in 15 subjects during the study; 5 and 7 adverse drug reactions from the 5 and 6 subjects were considered to probably be related to the test and reference treatments respectively. All adverse drug reactions were in line with those known for the reference drug. All subjects recovered fully with no sequelae. A FDC of amlodipine adipate/valsartan and amlodipine besylate/ valsartan combination tablets met the regulatory criteria for bioequivalence. In addition, no significant difference was observed in the safety assessments between two treatments. Thus, the newly developed FDC of amlodipine adipate/valsartan seems to be interchangeable with amlodipine besylate valsartan combination.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Objective: The efficacy and safety of statins have been studied in a number of clinical trials and epidemiological studies. In recent years, the Medicine and Healthcare Products Regulatory Agency (MHRA) has assessed the evidence available on the following adverse reactions associated with the use of statins: sleep disturbances, memory loss, micturition disorders (problems with urination), sexual disturbances, depression, and interstitial pneumopathy. However, the association between statin use and the risk of these adverse reactions remains unclear. To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) or the disorder causing LUTS, we carried out data mining using a prescription database. Methods: A large organized database of prescriptions constructed by a database vendor was used in the study. Symmetry analysis was used to identify the risk of LUTS after using statins over the period January 2006 to August 2013. Statin use in combination with drugs administered for storage LUTS was examined by prescription sequence symmetry analysis (PSSA). Results: A significant association between statins and drugs for storage LUTS was found, with adjusted sequence ratios (ASRs) of 1.21 (95% CI, 1.00 - 1.46), 1.19 (95% CI, 1.04 - 1.38), and 1.17 (95% CI, 1.05 - 1.30) for intervals of 91, 182, and 365 days, respectively. In the analyses of individual statins, significant associations were found only for pravastatin. Significant associations with individual drugs for storage LUTS were found for solifenacin succinate with ASRs of 1.36 (95% CI, 1.02 - 1.81), 1.48 (95% CI, 1.19 - 1.84), and 1.47 (95% CI, 1.25 - 1.73) for intervals of 91, 182, and 365 days, for flavoxate hydrochloride with an ASR of 1.56 (95% CI, 1.13 - 2.17) at an interval of 182 days, and for oxybutynin hydrochloride with ASRs of 2.06 (95% CI, 1.11 - 3.94) and 1.71 (95% CI, 1.09 - 2.72) at intervals of 182 and 365 days. Significant associations with gender were found only in females with ASRs of 1.25 (95% CI, 1.04 - 1.51) and 1.23 (95% CI, 1.07 - 1.41) at intervals of 182 and 365 days, respectively. Conclusions: Analysis of the prescription database showed significant association for storage LUTS in statin users.
    International journal of clinical pharmacology and therapeutics 07/2014;
  • International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Objective: Glycopyrronium (NVA237), a once-daily long-acting muscarinic antagonist, has recently been approved for the treatment of patients with chronic obstructive pulmonary disease (COPD). This study evaluated the effect of glycopyrronium on the QT interval and other cardiac parameters in healthy subjects. Methods: This randomized, partially blinded, single-dose, placebo- and positive- (moxifloxacin) controlled, three-way cross-over study investigated the effect of a single inhaled supra-therapeutic dose (8-fold clinical dose in COPD patients) of 400 µg glycopyrronium on the Fridericia-corrected QT interval (QTcF; primary objective), Bazettcorrected QT interval (QTcB), heart rate, blood pressure, pharmacokinetics (PK), safety, and tolerability. Results: A total of 73 healthy male (n = 35) and female (n = 38) subjects, aged between 18 and 45 years, were randomized. Glycopyrronium did not cause significant QTcF prolongation compared to placebo. The largest time-matched mean difference to placebo was 2.97 ms at 5 minutes, with the upper limit of the two-sided 90% confidence interval (CI) being 4.80 ms, excluding a relevant QT effect as defined by the ICH E14 guideline. Glycopyrronium had a slight bradycardic effect with a mean change of -2.88 (90% CI: -3.78, -1.99) beats per minutes (bpm) and a maximum of -5.87 (90% CI: -7.82, -3.92) bpm at 5 hours post-inhalation. No clinically relevant effects were seen on QTcB, other electrocardiogram (ECG) intervals, or blood pressure. Maximum plasma concentration (Cmax) of glycopyrronium was achieved shortly after inhalation (median tmax = 7 minutes). All the treatments were well tolerated with no serious adverse events. Conclusion: A supra-therapeutic dose of glycopyrronium had a favorable cardiovascular safety profile with no clinically relevant effect on QT interval.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Purpose: Lobaplatin, heptaplatin, and dicycloplatin are three new platinum drugs. The aim of this study is to investigate the chemosensitivity of resistant colon cancer cell lines to these three drugs. Methods: Eight resistant colon cancer cell lines (four oxaliplatin-resistant colon cancer cell lines and four irinotecan-resistant colon cancer cell lines) were cultured in 96-well plates. Lobaplatin, heptaplatin, and dicycloplatin were added in various concentrations. IC50 was determined by MTT assay and the results were confirmed by CCK-8 assay. A cell death detection ELISA assay was performed to quantitate the apoptotic index by detecting the histone-associated DNA fragments generated by the apoptotic cells. Results: Lobaplatin and heptaplatin had an inhibiting effect in all resistant cell lines, dicycloplatin demonstrate only weak antitumor activity in vitro. Conclusions: We confirmed the efficacy of two platinum drugs to oxaliplatin/ irinotecan-resistant colon cancer cell lines, suggesting these two drugs could be considered for improving the control of recurrent colon cancer following initial therapy with oxaliplatin and irinotecan.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Objective: Co-administration of anti-hypertension and anti-diabetic drugs is common in clinical settings. Methods: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Results: Metabolism of losartan by recombinant CYP2C9* 1, CYP2C9*3, CYP2C9*13, and CYP2C9* 16 was inhibited by glimepiride competitively with IC50 values of 0.669 ± 0.055 µM, 0.424 ± 0.032 µM, 2.557 ± 0.058 µM, and 0.667 ± 0.039 µM, respectively. The inhibitory effect of glimepiride on losartan metabolism by CYP2C9*13 was marginal. The apparent Ki value of glimepiride with CYP2C9*3 (0.0416 ± 0.0059 µM) was significantly lower than with CYP2C9*1 (0.1476 ± 0.0219 µM) and CYP2C9*16 (0.2671 ± 0.0456 µM). On the other hand, losartan weakly inhibited the hydroxylation of glimepiride by P450 2C9 enzymes competitively. The potencies for inhibition of glimepiride hydroxylation were determined to be CYP2C9*1 ~ CYP2C9*3 ~ CYP2C9*16 > CYP2C9*13 by 4 µM losartan. No significant inhibition was observed when 0.5 µM losartan was used. Conclusions: Given these results, the potential inhibition of losartan metabolism by CYP2C9*3, CYP2C9*13, and CYP2C9*16 in vivo by glimepiride deserves further investigation. These results may provide valuable information for optimizing the anti-hypertension efficacy of losartan when glimepiride is co-administered to patients.
    International journal of clinical pharmacology and therapeutics 07/2014;
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    ABSTRACT: Relapse of cancer months or years after an apparently successful therapy is probably caused by cancer stem cells (CSCs) due to their intrinsic features like dormant periods, radiorefraction, and acquired multidrug resistance (MDR) phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack of currently efficacious interventions remains a major problem in the treatment of malignancies, together with the inability of existing drugs to destroy specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory extracranial tumors in infants with very low survival rates. So far, no effective cytostatics against this kind of tumors are clinically available. Therefore, we have put much effort into the development of agents to efficiently combat this malignancy. For this purpose, we tested several compounds isolated from Cuban propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which expressed several characteristics of tumor-initiating cells both in in-vitro and in-vivo models. Some small molecules such as flavonoids and polycyclic polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC cycles and identified employing mass spectrometry and NMR spectroscopic techniques. Their cytotoxicity was first screened in sensitive cell systems by MTT proliferation assays and afterwards studied in less sensitive neuroblastoma iCSC models. We found several compounds with considerable anti-iCSC activity, most of them belonging to the PPAP class. The majority of the compounds act in a pleiotropic manner on the molecular biology of tumors although their specific targets remain unclear. Nevertheless, two substances, one of them a flavonoid, induced a strong disruption of tubulin polymerization. In addition, an unknown compound strongly inhibited replicative enzymes like toposimerases I/II and DNA polymerase. Here, we report for the first time cytotoxic activities of small molecules isolated from Caribbean propolis which could be promising therapeutics or lead structures against therapy-refractory neuroblastoma entities.
    International journal of clinical pharmacology and therapeutics 06/2014;
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    ABSTRACT: Objective: To compare the respiratory and circulatory parameters between intranasal and intravenous dexmedetomidine in gastroscopy. Methods: 60 patients undergoing elective gastroscopy were randomly divided into group D1 and D2. Dexmedetomidine (0.5 µg/kg, 1 mL) and normal saline (NS, 1 mL) were given by intranasal route 40 minutes before induction, and then NS (20 mL) and dexmedetomidine (0.5 µg/kg, 20 mL) were given intravenously 10 minutes before induction, respectively, in groupsD1 and D2. Propofol (1.5 - 2 mg/kg) was used for induction. Heart rate (HR), meanarterial pressure (MAP), pulse oxygen saturation(SpO2), and respiratory rate (RR) were monitored. The latent period of falling asleep, the duration of gastroscopy, the time of awakening, and the total dose of propofol consumption were also recorded. Postoperative sedation scale and adverse reactionswere observed. Results: One patient in group D1 was excluded from the study due to atrioventricular block. The HR and SpO2 were significantly lower, but RR was significantly higher in group D2 than in group D1(all p < 0.05). The time of awakening was significantly longer and the rates of respiratory depression were significantly higher in group D2 than in group D1 (all p < 0.05) There were no significant differences in other parameters between both groups. Conclusion: Intranasal dexmedetomidine is a new, safe, and effective approach for gastroscopy because it has more stable respiratory and circulatory parameters and less adverse reactions than intravenous dexmedetomidine.
    International journal of clinical pharmacology and therapeutics 06/2014;
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    ABSTRACT: Objective: Adherence of patients to therapy is a major determinant of therapeutic success, which is not included in most clinical studies. This is especially true for chronic diseases with few subjective symptoms, such as osteoporosis. The aim of our study was to describe and to analyze the therapeutic adherence to several widely used anti-osteoporotic medications in real-world medicine in Slovakia. Methods: Using a retrospective approach, data about drug prescriptions for 8,223 patients from 3 consecutive years were analyzed regarding complianceand persistence. Compliance was measured as medication possession ratio-ratio between the supply of the drugs in the treatment time according to the prescriptions and the time of observation. Persistence was assessed as the percentage of patients who used the drug without a gap for the given time period. Results: The average compliance was 70%, 59%, and 4% for 6, 12, and 24 months, respectively. Average persistence was very low with 54%, 42%, and 22% for 6, 12, and 24 months, respectively. Total average persistence was only 9.8 months. Medications with lower frequency of application tended to be associated with higher adherence. Conclusion: In conclusion, the therapeutic adherence to anti-osteoporotic treatments varies between the available drugs and drug regimens. In general, the adherence is very low but comparable to previously published studies from other countries. This variability of adherence should be considered in clinical decision making together with the variability of therapeutic efficiency found in clinical studies.
    International journal of clinical pharmacology and therapeutics 06/2014;
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    ABSTRACT: Objectives: In this study, we attempt to explore the feasibility of alternative dosing regimens of etanercept in patients with rheumatoid arthritis (RA) using pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulation. Methods: All data used for estimation of PK/PD model parameters were collected from previously published literatures. American College of Rheumatology (ACR) 20/50/70 response rate and a disease activity score in 28 joints (DAS28) was selected as the principal clinical endpoint for further PK/PD modeling. The cumulative AUC (area under the concentration-time curve) of etanercept for different dosing regimens was calculated based on the final PK model and was then linked to the time course of clinical endpoints. Ten different dosing regimens were simulated in this study. Results: The PK model that best fit the serum concentration-time data for etanercept was a one-compartment model with first order absorption and elimination. Based on the PK/PD analysis, the relationship between the predicted cumulative AUC of etanercept to the ACR 20/50/70 response rate and DAS28 score was well characterized by Emax logistic and inhibitory Emax model, respectively. In our simulations, the following dosing regimens that are equally effective to current recommended dosage of 25 mg twice weekly (b.i.w.): (1) 25 mg once weekly (q.w.); (2) 50 mg every 2 weeks (q2w); (3) 25 mg b.i.w. for 3 months and 25 mg q2w thereafter; and (4) 50 mg q.w. for 3 months and 50 mg q2w thereafter. Conclusion: In this study, the clinical data was well described by the models developed, and several alternative dosing regimens were proposed. Further clinical studies in patients are still needed to confirm our findings.
    International journal of clinical pharmacology and therapeutics 06/2014;
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    ABSTRACT: Objectives: A modified insulintolerance test (ITT) can be used to simulate a physiological stress state through the induction of controlled hypoglycemia in healthy volunteers. This allows for evaluation of hypothalamic-pituitary-adrenocortical axis response to stress via a surge in cortical release. However, a consequence of severe, prolonged hypoglycemia is QT interval prolongation. The aim of this analysis was to confirm that blood glucose lowering to 60 mg/dL (previously identified as adequate for inducing stress) has low risk of inducing clinically significant QT prolongation. Materials and methods: Continuous ECG monitoring was conducted as a planned substudyof an open-label, 2-period study involving 18 healthy male subjects. The QTcF response to hypoglycemia was measured over 2 identical periods, ~ 7 days apart. Results: An indirect- response model adequately described the pharmacological relationship between blood glucose and QTcF intervals over the time-course of the ITT. The model correctly identified the steep glucose-QT relationship as an on-off response with a large Hill coefficient of 59 and the threshold glucose, EC50, as ~ 57 mg/dL with narrow between-subject variability of 10%. Simulated QTcF profiles over the course of an ITT did not demonstrate any QTcF interval changes of clinical concern, defined as QTcF observation > 500 ms, if hypoglycemia did not reach below 60 mg/dL. The statistical prediction that the chance of a mean QTcF observation > 500 ms was < 0.0001. Conclusions: Results support that an ITT maintained at or above 60 mg/dL is unlikely to cause QT prolongation in healthy volunteers and does not warrant continuous ECG monitoring in this group of subjects.
    International journal of clinical pharmacology and therapeutics 06/2014;
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    ABSTRACT: Objective: This study was to establish the population pharmacokinetic (PPK) model of pharmacologically active metabolite of oxcarbazepine (OXC) and to estimate PPK parameters for the optimal individuation administration of OXC inChinese children with epilepsy. Methods: The pharmacologically active metabolite, 10-monohydroxy derivative of OXC (MHD)was used as the analytical target for monitoring therapy of OXC. A total of 840 MHD serum samples from 466 children with epilepsy were analyzed using high-performance liquid chromatography with UV detection. Patients' clinical data were retrospectively collected. Population pharmacokinetics analysis was performed using a non-linear mixed-effect model with Phoenix NLME 1.2. Pharmacokinetic parameters were estimated according to a one-compartment model with first-orderabsorption and elimination. Effects of age,gender, total body weight (TBW), daily doseper weight (DDPW) and use of concomitantantiepileptic drugs (AEDs) were analyzed.Bootstrap and predictive check were used simultaneouslyto validate the final populationpharmacokinetics models. Results: The finalPPK model of MHD was: Ka = 0.645 h-1, V(L) = (11.3 + (age - 90.5) x 0.0282 + (TBW - 25.0) x 0.402) x e0.0689, CL (L/h) = (0.557 + (DDPW - 20.8) x 0.00367 + (gender) x (-0.0636)) x e0.120. The final PPK model was demonstrated to be suitable and effective by the bootstrap and predictive check. Conclusions: A PPK model of MHD in Chinesechildren with epilepsy was successfully established. PPK parameters of MHD could be predicted accurately by this model. Thismodel may be very useful for establishingindividual dosage guidelines of OXC in Chinesechildren with epilepsy.
    International journal of clinical pharmacology and therapeutics 06/2014;
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    ABSTRACT: Aim: The objective of the present study was to develop population pharmacokinetic models for olmesartan medoxomil and hydrochlorothiazide and to investigatem the influence of demographic factors on these population pharmacokinetics. Methods: Plasma concentrations of olmesartan medoxomil and hydrochlorothiazide were measured in 41 healthy volunteers enrolled in our bioequivalence study by LC-MS/MS following oral administration of an olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) fixed-dose combination tablet. This data and covariates were subjected to nonlinear mixed-effect modeling analysis using the NONMEM software. Evaluation featured a visual predicted check and bootstrapping. Results: The distributions of olmesartan medoxomil and hydrochlorothiazide were best fitted using a two-compartment model with no lag time and first-order elimination. When analyzing hydrochlorothiazide kinetics, we found that TCHO and CL/F were correlated, while. HB and Ka influenced olmesartan medoxomil modeling. All evaluations indicated that the pharmacokinetic profiles of olmesartan medoxomil and hydrochlorothiazide were adequately described using our PPK model. Conclusions: This study indicates that demographic factors influence the inter-individual variability in the disposition of the combination drug, and it might be more useful to apply it to the PK of olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) FDC tablets administered to patients with hypertension.
    International journal of clinical pharmacology and therapeutics 05/2014;
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    ABSTRACT: Pregabalin, an analogue of the gamma-aminobutyric acid mammalian neurotransmitter and its structurally related compound gabapentin are known as alpha2delta ligands. They might act as inhibitory modulators of neuronal excitability that reduce ectopic neuronal activation of hyperexcited neurons while normal activation remains unchanged. However, the interaction with Ca2+ channel alpha2delta subunit is not sufficient to account for the broad clinical spectrum of pregabalin effects including the abuse potential. Pregabalin is approved for the treatment of partial epilepsy; generalized anxiety disorder; peripheral< and central neuropathic pain and fibromyalgia. Its prescribing is rapidly increasing and total sales of the drug worldwide reached 4.6 billion US$ in 2012. Since entering widespread clinical use, reports of pregabalin abuse appeared more often, usually involving individuals with a history of abuse of other medications. The purpose of this mini review is to present available published data signaling pregabalin’s abuse liability reflecting on the pharmacological characteristics that might enable this agent to trigger addictive behaviors.
    International journal of clinical pharmacology and therapeutics 05/2014;

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