Volume 54, No. 8/2016(August)
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Original Research
Treatment of depression in patients with cardiovascular diseases by German psychiatrists
Marcel Konrad, Louis Jacob, Michael A. Rapp, and Karel Kostev
Price
42.00 $
Page No. 557
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (557-563)
Treatment of depression in patients with cardiovascular diseases by German psychiatrists
Marcel Konrad1, Louis Jacob2, Michael A. Rapp3, and Karel Kostev4
1Fresenius University of Applied Sciences, Idstein, Germany, 2Department of Biology, École Normale Supérieure de Lyon, Lyon, France, 3Department of Social and Preventive Medicine, University of Potsdam, Potsdam, and 4IMS Health, Frankfurt am Main, Germany
Objective: To estimate the prevalence and the type of antidepressant medication prescribed by German psychiatrists to patients with depression and cardiovascular diseases (CVD). Methods: This study was a retrospective database analysis in Germany using the Disease Analyzer Database (IMS Health, Germany). The study population included 2,288 CVD patients between 40 and 90 years of age from 175 psychiatric practices. The observation period was between 2004 and 2013. Follow-up lasted up to 12 months and ended in April 2015. Also included were 2,288 non-CVD controls matched (1 : 1) to CVD cases on the basis of age, gender, health insurance coverage, depression severity, and diagnosing physician. Results: Mean age was 68.6 years. 46.2% of patients were men, and 5.9% had private health insurance coverage Mild, moderate, or severe depression was present in 18.7%, 60.7%, and 20.6% of patients, respectively. Most patients had treatment within a year, many of them immediately after depression diagnosis. Patients with moderate and severe depression were more likely to receive treatment than patients with mild depression. There was no difference between CVD and non-CVD in the proportion of patients treated. Nonetheless, CVD patients received selective serotonin reuptake inhibitors / serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) significantly more frequently. Conversely, patients without CVD were more often treated with TCA. Conclusion: There was no association between CVD and the initiation of depression treatment. Furthermore, CVD patients received SSRIs/SNRIs more frequently.Correspondence to:
Prof. Dr. rer. med. Karel Kostev
Epidemiology, Real World Evidence Solutions
IMS HEALTH GmbH & Co. OHG
Darmstädter Landstraße 108
60598 Frankfurt am Main, Germany
Email: [email protected]
Original Research
Safety and effectiveness of antifungal prophylaxis in preventing fungal infection after liver transplantation: a meta-analysis of randomized clinical trials
Tonghai Xing, Lin Zhong, and Zhihai Peng
Price
42.00 $
Page No. 564
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (564-571)
Safety and effectiveness of antifungal prophylaxis in preventing fungal infection after liver transplantation: a meta-analysis of randomized clinical trials
Tonghai Xing, Lin Zhong, and Zhihai Peng
Department of General Surgery, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Background: Fungal infections are widely recognized as a complication of liver transplantation, and their prevention and treatment are a challenge for clinicians. Methods: This was a randomized clinical trial (RCT)-based meta-analysis investigating the safety and effectiveness of antifungal prophylaxis in preventing fungal infection after liver transplantation. Studies published before December 2013 were searched for in several databases. Patients who underwent antifungal prophylaxis were included in the treatment group. Studies that met the inclusion criteria were included in this meta-analysis. Quality assessment, data extraction, and statistical analysis were performed. Results: A total of 342 articles was identified, and 7 eligible articles were included in the present study. The pooled estimate of the OR for all-cause mortality was 0.82 (95% confidence interval (CI): 0.51 – 1.30, p = 0.39). The pooled estimate of the OR of fungal infection-related mortality was 0.29 (95% CI: 0.11 – 0.75, p = 0.01), which was significantly different between the treatment and control groups. The pooled estimate of the OR of defined invasive fungal infection was 0.41 (95% CI: 0.26 – 0.63, p < 0.001). The OR of adverse events was 1.20 (95% CI: 0.68 – 2.12, p = 0.53). Conclusion: This meta-analysis suggests that antifungal prophylaxis could effectively reduce the risk of invasive fungal infections in patients who underwent liver transplantation. Overall mortality rate was not different with prophylaxis, according to current evidence. This needs to be further investigated.Correspondence to:
Zhihai Peng
Department of General Surgery
Shanghai First People’s Hospital
School of Medicine, Shanghai Jiao Tong University
Shanghai 310000, China
Email: [email protected]
Original Research
Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH
Anne Schmitt-Hoffmann, Amit Desai, Donna Kowalski, Helene Pearlman, Takao Yamazaki, and Robert Townsend
Price
42.00 $
Page No. 572
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (572-580)
Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH
Anne Schmitt-Hoffmann1, Amit Desai2, Donna Kowalski2, Helene Pearlman2, Takao Yamazaki2, and Robert Townsend2
1Basilea Pharmaceutica International Ltd., Basel, Switzerland, and 2Astellas Pharma Global Development, Northbrook, IL, USA
Objective/methods: Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Results: Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Conclusions: Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.Correspondence to:
Robert Townsend, PhD
Global Clinical Pharmacology & Exploratory Development Science
Astellas Pharma US, Inc
1 Astellas Way, Northbrook, IL 60062, USA
Email: [email protected]
Original Research
Clinical pharmacist interventions on a Chinese neurology ward: a 2-year service evaluation
Yunzhen Hu, Meiling Cao, Danhua Xu, Jianwen Wang, and Xiaoyang Lu
Price
42.00 $
Page No. 581
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (581-586)
Clinical pharmacist interventions on a Chinese neurology ward: a 2-year service evaluation
Yunzhen Hu1, Meiling Cao2, Danhua Xu1, Jianwen Wang2, and Xiaoyang Lu1
1Department of Pharmacy and 2Department of Neurology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
A prospective observational study of clinical pharmacist interventions was conducted over a 2-year period from November 2012 to October 2014 to evaluate the clinical activity of pharmacists in the care they provide to patients and to promote safe and effective medication therapy by quantifying medicine-related interventions on a Chinese neurology ward. All pharmacist interventions made in the department of neurology were recorded, categorized, and assessed for potential patient harm if the intervention had not taken place. The quantity, outcomes, and potential severity of clinical pharmacists’ interventions were recorded. 619 interventions were made in 385 patients over the 2-year observational period. The mean severity of potential harm assessment was 3.7 (1.12), range 0.8 – 7.0. 87 of the 619 interventions (14.0%) were classified as medication errors. The results of the clinical pharmacist intervention study demonstrated that pharmacists play an important role in the care of neurological patients by improving patient care and reducing clinical risk.Correspondence to:
Prof. Xiaoyang Lu
Department of Pharmacy
The First Affiliated Hospital, College of Medicine
Zhejiang University, Hangzhou, China
Email: [email protected]
Original Research
Dose regimens for Chinese adult liver transplant recipients according to the genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in recipients and donors
Liqin Zhu, Shasha Liao, Nan Wang, Tingyue Ge2, Jianwei Yang, Gaoqi Xu, Jianhai Wang, Keqiu Li, and Guang Li
Price
42.00 $
Page No. 587
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (587-596)
Dose regimens for Chinese adult liver transplant recipients according to the genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in recipients and donors
Liqin Zhu1*, Shasha Liao2*, Nan Wang3, Tingyue Ge2, Jianwei Yang2, Gaoqi Xu2, Jianhai Wang2, Keqiu Li2, and Guang Li2
1Department of Pharmacy, Tianjin First Central Hospital, 2Basic Medical College, Tianjin Medical University, and 3Department of Pharmacy, Tianjin Third Central Hospital, China
Objective: Genetic polymorphisms of the P450 2C9 enzyme (CYP2C9), CYP2C19 and CYP3A5 gene are known to affect the metabolism of many drugs applied in liver transplant recipients, such as warfarin, voriconazole, and tacrolimus. The aim of this study was to recommend dose regimens for the liver recipients based on CYP2C9, CYP2C19, and CYP3A5 genotypic combinations of liver transplant recipients and their donors. Methods: 91 adult Han Chinese liver transplant recipients who underwent orthotopic liver transplantation at Tianjin First Central Hospital, China, between 2013 and 2014 were included in this study. CYP2C9*2, CYP2C9*3, CYP2C19* 2, CYP2C19*3 and CYP3A5*3, in both liver recipients and their grafted liver were tested by polymerase chain reaction-restriction fragment length polymorphism. The dose regimens for the liver recipients were recommended based on CYP genotypic combinations of the recipients and their donors. Results: In the liver transplant recipients, the frequencies of CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP3A5*3 were found to be 2.75%, 4.40%, 0%, 24.18%, and 75.27%, respectively. Allele frequencies were significantly different for CYP2C9*2, CYP2C19*2, and CYP2C19* 3 (p < 0.001) when comparing the recipients with Chinese, Eastern Asians and Caucasians populations. Most dose regimens of drugs, especially of immunosuppressive drugs, should be adjusted according to the variant metabolism activity affected by the genetic polymorphisms in both recipients and their grafted liver. Conclusion: The dose regimens would present considerable intraand inter-patient variability in liver transplant recipients since the genetic polymorphisms of P450 enzyme in their grafted liver might complicate the metabolism of drugs in liver transplant recipients. Giving careful consideration to the CYP genotypic combinations of transplant recipients and donors in clinical dose regimens could optimize outcomes.
*Authors contributed equally to this work.Correspondence to:
Dr. Guang Li
Basic Medical College, Tianjin Medical University
22# Qixiangtai Road, Heping District, Tianjin 300070, China
Email: [email protected]
Original Research
Overuse of proton pump inhibitors for stress ulcer prophylaxis in Jordan
Mohammad A.Y. Alqudah, Sayer Al-azzam, Karem Alzoubi, Mohammad Alkhatatbeh, and Neda’ Rawashdeh
Price
42.00 $
Page No. 597
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (597-602)
Overuse of proton pump inhibitors for stress ulcer prophylaxis in Jordan
Mohammad A.Y. Alqudah, Sayer Al-azzam, Karem Alzoubi, Mohammad Alkhatatbeh, and Neda’ Rawashdeh
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
Objective: To determine the frequency of inappropriate proton pump inhibitor (PPI) prescriptions during hospitalization for stress ulcer prophylaxis on the general medical ward in a tertiary Jordanian hospital. Materials and methods: A retrospective chart review was executed on 236 patient admissions prescribed any PPI in a tertiary Jordanian hospital. For each patient, a detailed range of demographic and clinical variables was recorded. Patient’s clinical variables were clustered into major vs. minor criteria for using PPIs in stress ulcer prophylaxis according to the American society of health-system pharmacists’ (ASHP) therapeutic guidelines on stress ulcer prophylaxis. Results: The 236 patients (51% females) had a mean age of 52 ± 18.1 years. Approximately 56% of the patients were using PPIs before admission. All our patients started PPI use for stress ulcer prophylaxis. Of these, 86% were unnecessary and should be avoided since they do not have at least 1 major or 2 minor indications. Previous PPI use before admission or the presence of one risk factor for stress ulcer motivated initiation of therapy predominately. Recent gastrointestinal (GI) ulcer/bleeding (23%) and coagulopathy (8%) were the main major indications. High-dose corticosteroid (24%) was the most frequent minor indication. Conclusions: The high frequency of inappropriate PPI prescriptions in stress ulcer prophylaxis for inpatients is a major issue in Jordan. Following the current recommended therapeutic guidelines of stress ulcer prophylaxis could minimize the overuse of PPIs in inpatient settings and thus decrease both the possible safety issues of PPIs and the economic burden on the health-care system.Correspondence to:
Mohammad A.Y. Alqudah, PharmD, PhD
Department of Clinical Pharmacy
Faculty of Pharmacy
Jordan University of Science and Technology
Irbid, 22110, Jordan
Email: [email protected]
Original Research
miRNA-124 modulates lung carcinoma cell migration and invasion
Zhengliang Li, Xi Wang, Wenhui Li1, Lun Wu, Li Chang, and Hong Chen
Price
42.00 $
Page No. 603
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (603-612)
miRNA-124 modulates lung carcinoma cell migration and invasion
Zhengliang Li1*, Xi Wang2*, Wenhui Li1, Lun Wu3, Li Chang1, and Hong Chen4
1Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, 2Special Medical Treatment, The Second Affiliated Hospital of Kunming Medical University, Kunming, 3Department of Radiology, The Second People’s Hospital of Yunnan Province, Kunming, and 4Department of Oncology, Kunming General Hospital of Chengdu Military Region, Kunming, China
Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide. Recently, accumulating studies have evidenced that microRNAs (miRNAs) contribute to the carcinogenesis of lung cancer through acting as either oncogenes or tumor suppressors. The purpose of our study was to investigate the functional role of miR-124 in lung cancer. Methods: The expression of miR-124 was assessed by real-time RT-PCR in non-small cell lung cancer (NSCLC) tissues in comparison to its adjacent normal tissues. After transfection with miR-124 Mimics or negative controls into A549 cells, migration and invasion assays, apoptosis, and cell viability were evaluated. Luciferase reporter assay and RT-PCR were performed to explore whether zinc finger e-box binding homeobox 1 (ZEB1) was a target of miR-124. Further, the effects of miR-124 Mimic on migration and invasion were assessed after overexpression of ZEB1. Results: MiR-124 expression was significantly down-regulated in NSCLC tissues compared to the normal tissue. In in-vitro study, overexpression of miR-124 in A549 cells suppressed cell migration and invasion activity, decreased expression of vimentin, but increased expression of E-cadherin and induced apoptosis. Luciferase reporter assay ensured that ZEB1 was a direct target of miR-124 and was negatively regulated by miR-124. Overexpression of ZEB1 could reverse the effect of miR-124 Mimic on the migration and invasion of the cells. Conclusion: The results suggests that miR-124 inhibits lung cancer cell migration and invasion through suppressing epithelial-mesenchymal transition (EMT) and inducing apoptosis of the lung cancer cells.
*Zhengliang Li and Xi Wang are co-first authors.Correspondence to:
Dr. Wenhui Li
Department of Radiation Oncology
The Third Affiliated Hospital of Kunming Medical University
Kunming, Yunnan Province, 650118, China
or
Dr. Hong Chen Department of Oncology
Kunming General Hospital of Chengdu Military Region
Kunming 650118, China
Email: [email protected] or [email protected]
Original Research
The effects of apremilast on the QTc interval in healthy male volunteers: a formal, thorough QT study
Maria Palmisano, Anfan Wu, Mahmoud Assaf, Liangang Liu, C. Hyung Park, Ishani Savant, Yong Liu, and Simon Zhou
Page No. 613
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (613-621)
The effects of apremilast on the QTc interval in healthy male volunteers: a formal, thorough QT study
Maria Palmisano1, Anfan Wu2, Mahmoud Assaf1, Liangang Liu1, C. Hyung Park1, Ishani Savant3, Yong Liu1, and Simon Zhou1
1Celgene Corporation, Summit, NJ, USA, 2Novartis Institutes for BioMedical Research, Shanghai, China, and 3Bristol-Myers Squibb, Princeton, NJ, USA
Objective: This study was conducted to evaluate the effect of apremilast and its major metabolites on the placebocorrected change-from-baseline QTc interval of an electrocardiogram (ECG). Materials and methods: Healthy male subjects received each of 4 treatments in a randomized, crossover manner. In the 2 active treatment periods, apremilast 30 mg (therapeutic exposure) or 50 mg (supratherapeutic exposure) was administered twice daily for 9 doses. A placebo control was used to ensure doubleblind treatment of apremilast, and an openlabel, single dose of moxifloxacin 400 mg was administered as a positive control. ECGs were measured using 24-hour digital Holter monitoring. Results: The two-sided 98% confidence intervals (CIs) for ΔΔQTcI of moxifloxacin completely exceeded 5 ms 2 – 4 hours postdose. For both apremilast dose studies, the least-squares mean ΔΔQTcI was < 1 ms at all time points, and the upper limit of two-sided 90% CIs was < 10 ms. There were no QT/QTc values > 480 ms or a change from baseline > 60 ms. Exploratory evaluation of pharmacokinetic/pharmacodynamic data showed no trend between the changes in QT/QTc interval and the concentration of apremilast or its major metabolites M12 and M14. Conclusions: Apremilast did not prolong the QT interval and appears to be safe and well tolerated up to doses of 50 mg twice daily.Correspondence to:
Maria Palmisano, MD
Translational Development-Clinical Pharmacology
Celgene Corporation
86 Morris Avenue, Summit, NJ 07901, USA
Email: [email protected]
Original Research
The rs662 polymorphism of paraoxonase 1 affects the difference in the inhibition of butyrylcholinesterase activity by organophosphorus pesticides in human blood
Dae Cheol Nam, Yu Mi Ha, Min Kyu Park, and Sung Kweon Cho
Price
42.00 $
Page No. 622
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (622-627)
The rs662 polymorphism of paraoxonase 1 affects the difference in the inhibition of butyrylcholinesterase activity by organophosphorus pesticides in human blood
Dae Cheol Nam1, Yu Mi Ha2, Min Kyu Park2, and Sung Kweon Cho3
1Department of Orthopaedic Surgery, Gyeongsang National University College of Medicine and Gyeongsang National University Hospital, Jinju, 2Department of Clinical Pharmacology, Dong-A University Medical Center; Department of Pharmacology, College of Medicine, Dong-A University, Busan, and 3Armed Forces Medical Research Institute, Daejeon, Republic of Korea
Objectives: Organophosphorus pesticides (OPs) are a human health hazard. OPs inhibit acetylcholinesterase (AChE) at nerve endings and accumulate acetylcholine (ACh) at these sites. High levels of ACh and long exposure promote cholinergic crisis. The hydrolysis of OPs by serum paraoxonase 1 (PON1) plays a role in cholinergic crisis in humans. Human serum PON1 can break down organophosphate before binding to ChE. We investigated the effect of PON1 polymorphisms on AChE activity after OP treatment. Methods: 50 healthy volunteers were randomly recruited with informed consent. We investigated butyrylcholinesterase (BuChE) activity changes in plasma as a biomarker of AChE after OP treatment in human blood samples immediately following blood sampling. After the standardization of BuChE activity in human blood, we correlated changes in BuChE activity with changes in blood pH. We analyzed the PON1 polymorphisms (rs854560 and rs662) of 50 participants to retrospectively investigate the interindividual variability of changes in BuChE activity. Results: Changes in BuChE activity are strongly correlated with pH changes after OP treatment (R2 = 0.913). We used changes in pH as a surrogate marker for BuChE inhibition after OP treatment. OP treatment significantly decreased BuChE activity by 56.4 ± 5.1% (p < 0.001). The degree of BuChE inhibition was significantly different in the PON1 rs662 genotype (56.10 ± 4.74% vs. 57.96 ± 5.67% vs. 52.34 ± 1.51%; GG vs. GA vs. AA, respectively). Conclusion: Changes in pH can be used as a surrogate marker for the detection of BuChE inhibition after OP exposure. The rs662 polymorphism of PON1 may explain the inter-individual variability in BuChE inhibition.Correspondence to:
Sung Kweon Cho, MD, PhD
Armed Forces Medical Research Institute
90bun, Jaunro, Yuseong-gu, Daejeon, 305-878, Korea
Email: [email protected]
Original Research
Effects of cardiovascular drugs on TSH serum levels in patients on replacement therapy after thyroidectomy
Marija Andjelkovic, Slobodan Jankovic, Marina Mitrovic, Violeta Mladenovic, Ivana Nikolic, Ivanka Zelen, Milan Zaric, Petar Canovic, and Marko Folic
Price
42.00 $
Page No. 628
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (628-633)
Effects of cardiovascular drugs on TSH serum levels in patients on replacement therapy after thyroidectomy
Marija Andjelkovic1,2, Slobodan Jankovic3, Marina Mitrovic2, Violeta Mladenovic4, Ivana Nikolic2, Ivanka Zelen2, Milan Zaric2, Petar Canovic2, and Marko Folic3
1Department of Laboratory Diagnostics, Clinical Centre Kragujevac, 2Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, 3Department of Clinical Pharmacology, Clinical Centre Kragujevac and Faculty of Medical Sciences, University of Kragujevac, and 4Department of Internal Medicine, Faculty of Medical sciences, University of Kragujevac, Kragujevac, Serbia
Objective: Hypothyroidism is one of most common endocrine disorders resulting from deficiency of thyroid hormones. The aim of our study was to investigate whether cardiovascular drugs as well as gender, age, body-mass index, and habits, like smoking or drinking coffee affect thyroid-stimulating hormone (TSH) level in hypothyroid patients with thyroxine replacement therapy who suffer from cardiovascular disease. Materials: The study was conducted on 150 hypothyroid patients who underwent total thyroidectomy for benign reasons; they were divided into five treatment groups: levothyroxine only group and, according to the drugs they had in therapy alongside levothyroxine, the angiotensinconverting enzyme inhibitors group, the selective β-blockers group, the calcium antagonists group, as well as the nitrates group. A retrospective cohort study was conducted in the Clinical Center Kragujevac, Serbia, during the period of January 2012 to October 2014. All patients’ data were collected both from participants’ health records and questionnaires that patients completed, including data about habits, like smoking or drinking coffee. Results: TSH values were significantly higher in the group of patients with selective β-blockers in therapy alongside levothyroxine, compared to all the other study groups. The values of TSH level did not significantly differ among the other therapy groups. On the other hand, cigarette smoking was a risk factor that decreased TSH levels in patients on thyroid replacement therapy. Conclusions: Our study shows that selective β-1 blockers can increase, while cigarette smoking can decrease TSH serum levels in hypothyroid patients on thyroid-replacement therapy.Correspondence to:
Marija Andjelkovic, PhD
Department of Laboratory Diagnostics
Clinical Centre Kragujevac
Zmaj Jovina 30, Kragujevac, 34000, Serbia
Email: [email protected]
Viewpoint
Acetylsalicylic acid (ASA) – How much, how often, and when? A clinical-pharmacological perspective
Dieter Loew and Gustav G. Belz
Price
42.00 $
Page No. 634
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (634-639)
Acetylsalicylic acid (ASA) – How much, how often, and when? A clinical-pharmacological perspective
Dieter Loew1 and Gustav G. Belz2
1Sörgenloch and 2Wiesbaden, Germany
The dose of acetylsalicylic acid (ASA) commonly used in the prevention and treatment of arteriosclerotic angiopathies is equal to or less than 100 mg daily. This choice of dose is predominantly based on molecular-pharmacological findings showing an inhibition in synthesis of the prothrombotic thromboxane (TXB2) and an irreversible inhibition in blood platelet aggregation. However, an analysis of ASA dose-effect relationships for doses of 50 – 500 mg (PO and IV) shows that doses of ASA up to 100 mg daily produce only a small or moderate inhibition in collagen/epinephrine-induced platelet aggregation and have no significant effect on the important platelet factors, PF3 and PF4. Doses of ASA 300 – 500 mg, on the other hand, inhibit platelet aggregation almost completely and, in addition, produce a 50 – 70% inhibition in PF3 and PF4 lasting at least 24 hours. There is also evidence that doses of ASA above 100 mg daily markedly inhibit thromboxane synthesis for up to 24 hours and that doses of 500 mg daily produce a clinically relevant inhibition in platelet adhesion to vessel walls for up 72 hours and prevent procoagulatory shape changes for up to 12 hours. These findings suggest that a dose of ≥ 300 mg at intervals of 2 – 3 days would be more appropriate for primary and secondary prophylaxis of arteriosclerotic angiopathies and that the benefit-risk ratio would be greater because of the increased availability of mucoprotective prostaglandins, PGI2 (prostacyclin) and the gastroprotective, PGE2. Our viewpoint, predominantly based on findings with biomarkers, could serve as a basis for further randomized controlled studies.Correspondence to:
Prof. Dr. Dr. Dieter Loew
An der Residenz 5, 55270 Sörgenloch
Case Report
Life threatening biphasic adverse reactions to desmopressin: case report and review of the literature
Lijun Wang, Ruijun Chen, Fang Tian, Wei Wang, Li Wang, Baojun Yu, Xianwen Huang, Yuehui Zhang, Shengyuan Su, Guangnian Ma, and Kaichen Wang
Price
42.00 $
Page No. 640
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (640-644)
Life threatening biphasic adverse reactions to desmopressin: case report and review of the literature
Lijun Wang, Ruijun Chen, Fang Tian, Wei Wang, Li Wang, Baojun Yu, Xianwen Huang, Yuehui Zhang, Shengyuan Su, Guangnian Ma, and Kaichen Wang
Department of Critical Care Medicine, The Affiliated Bao’an Hospital of Southern Medical University, Shenzhen, China
Treatment with desmopressin diacetate arginine vasopressin (DDAVP) and its withdrawal are associated with side effects. We present a rare case of severe biphasic adverse reactions induced by DDAVP and its withdrawal in a 63-year-old female patient. A lump in the left axillary region was biopsied, and she received DDAVP after surgery. The following day, she lost consciousness, with foaming at the mouth and seizures. Hypotonic encephalopathy was considered. DDAVP was ceased, and she received electrolytes. On day 1, she displayed low blood pressure and increased urine output. She received DDAVP and dopamine as well as electrolytes. The patient was ambulatory on day 7 and was discharged without brain abnormalities on MRI. In conclusion, severe hyponatremia induced by DDAVP and massive polyuria and hypovolemic shock induced by DDAVP withdrawal are life-threatening conditions. This case underlines the need to be vigilant when administering DDAVP and to monitor for any side effects.Correspondence to:
Lijun Wang, MD, PhD
Deparment of Critical Care Medicine
The Affiliated Bao’an Hospital of Southern Medical University
Shenzhen 518101, China
Email: [email protected]
Case Report
Induced next-day somnolence in an elderly patient taking suvorexant concomitantly with diltiazem
Atsuko Shihyakugari, Satoko Hori, Akiko Miki, and Yasufumi Sawada
Price
42.00 $
Page No. 645
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (645-648)
Induced next-day somnolence in an elderly patient taking suvorexant concomitantly with diltiazem
Atsuko Shihyakugari1, Satoko Hori2,3, Akiko Miki3, and Yasufumi Sawada3
1Ain Pharmaciez Shikahama Branch, Tokyo, 2Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, and 3Laboratory of Drug Lifetime Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
Objective: To present the first case of induced next-day somnolence in a patient taking suvorexant concomitantly with diltiazem. Case summary: The patient was an 88-year-old female who had suffered from insomnia and anorexia, for which a psychiatric clinic had prescribed 1.5 mg/day aripiprazole and 15 mg/day suvorexant (both once daily at bedtime), which cured her insomnia. Subsequently, a different hospital prescribed diltiazem hydrochloride (100 mg, sustained-release, daily after breakfast) for treatment of hypertension. After starting diltiazem, the patient was unable to wake up in the morning and overslept by ~ 3 hours. On the third day of taking diltiazem, the patient, on the basis of her own judgment, took only half a tablet of suvorexant, and found that she was able to sleep, and there was no somnolence the following morning. As halving suvorexant tablets is an off-label usage, and lower-dose tablets are not available, her prescription was switched to 1-mg rilmazafone hydrochloride. Since then, her sleep disorder has not recurred. Discussion: Because suvorexant is metabolized by CYP3A4, next-day somnolence could have occurred as a result of increased plasma suvorexant concentration due to CYP3A4 inhibition by diltiazem. Conclusion: Elderly patients may suffer next-day somnolence if they concomitantly take suvorexant and sustained-release diltiazem hydrochloride, even if the diltiazem dose is low and there is a significant interval between the administration times of the two drugs. In order to avoid drug interaction, it may be desirable to switch from suvorexant to a different soporific that is not metabolized by CYP3A4.Correspondence to:
Professor Yasufumi Sawada
Laboratory of Drug Lifetime Management
Graduate School of Pharmaceutical Sciences
The University of Tokyo
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Bioavailability Section
Relative bioavailability between two teriparatide formulations in healthy volunteers
Javier Farías, Guillermo A. Keller, Mariana Papouchado, María C. Villa Etchegoyen, Marcelo E. Criscuolo, Roberto A. Diez, and Guillermo Di Girolamo
Price
42.00 $
Page No. 649
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 8/2016 (649-656)
Relative bioavailability between two teriparatide formulations in healthy volunteers
Javier Farías1, Guillermo A. Keller2, Mariana Papouchado1, María C. Villa Etchegoyen2, Marcelo E. Criscuolo1, Roberto A. Diez1, and Guillermo Di Girolamo2
1Biosidus S.A. and 2Department of Pharmacology, Second Chair of Pharmacology, School of Medicine, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
Objective: To compare the pharmacokinetics, relative bioavailability (RB), immunogenicity, and safety after a single dose of test or reference formulation of teriparatide in healthy human volunteers in order to demonstrate whether both products are similar. Research design and methods: We compared pharmacokinetic parameters, immunogenicity, and safety after a single dose of two formulations (Osteofortil® and Forteo®) of teriparatide in a randomizedsequence, open-label, two-period crossover study in 24 healthy volunteers. The washout period between formulations was 7 days. Blood samples were collected at baseline and 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150 minutes, and 3 and 4 hours after administration. Teriparatide concentrations were determined using ELISA. Adverse events were monitored. Results: Geometric mean (90% CI) Cmax for test and reference formulations were 165.86 (153.35 – 212.13) and 175.37 (164.04 – 221.04) pg/mL, the AUC0–t was 14,932 (5,275 – 15,752) and 14,153 (1,861 – 16,875) pg×min/mL, and the AUC0–∞ was 16,147 (15,047 – 18,799) and 15,467 (14,473 – 18,126) pg×min/mL, respectively. The test/reference ratios (90% CI) for Cmax, AUC0–t, and AUC0–∞ were 94.58% (85.29 – 104.87), 105.5% (97.77 – 113.84), and 104.4% (96.97 – 112.39), respectively No subject reported adverse events. Conclusion: Test formulation met pharmacokinetic criteria for bioequivalence.Correspondence to:
Guillermo Di Girolamo, MD, PhD
Department of Pharmacology, School of Medicine
Universidad de Buenos Aires, Argentina
Paraguay 2155, C1121ABG, Ciudad Autónoma de Buenos Aires, Argentina
Email: [email protected]
