Dustri Online Services

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (1-9)

Postmarketing pharmacovigilance of adverse drug reactions: the case of rosiglitazone in Mexico

Hortensia Reyes-Morales¹, Dolores Mino-León², Svetlana V. Doubova³ and Sergio Flores-Hernández⁴

¹Centro de Investigación en Sistemas de Salud, Instituto Nacional de Salud Pública, Morelos, ²Instituto de Geriatría, Institutos Nacionales de Salud, ³Unidad de Investigación en Epidemiología y Servicios de Salud “Centro Médico Nacional Siglo XXI” and ⁴Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Objective: Commercialization of rosiglitazone, an oral blood glucoselowering drug of the thiazolidinedione class, was recently suspended in Europe and significantly restricted in the United States due to a possibly increased risk of ischemic heart disease; the drug is still being marketed in Mexico. This study was aimed to analyze the post-marketing occurrence of adverse drug reactions (ADRs) with rosiglitazone when used in combination therapy in Mexican Type 2 Diabetes patients. Methods: A prospective observational study was conducted at a primary health-care clinic in Mexico City. Eligible subjects were adult patients with Type 2 diabetes inadequately controlled with maximal doses of oral monotherapy, in which one of two combined therapeutic schemes was prescribed: rosiglitazone/glibenclamide (R/G), or rosiglitazone/metformin (R/M). Patients’ blood pressure, weight, treatment adherence and occurrence of ADRs were monitored during a 6-month follow-up period. Results: 174 patients received treatment with R/M or R/G (112 and 62 patients, respectively). At least one ADR was observed in about 75%, of patients. Prior to the end of the follow-up period, moderate ADRs leading to discontinuation of the treatment occurred in 29.5% and 14.5% of patients treated with R/M and R/G, respectively. The ADRs most frequently observed were peripheral edema and moderate weight gain. Conclusions: The use of rosiglitazone in combination with other oral anti-diabetic drugs was associated with a high frequency of ADRs in Mexican patients with Type 2 diabetes. Post-marketing studies are relevant to identify drug-associated risks to patients in clinical practice.Correspondence to:
H. Reyes-Morales, MD, Msc, DrSc
Centro de Investigación en Sistemas de Salud
Av. Universidad No. 655
Col. Santa María Ahuacatitlán
Cuernavaca, Morelos 62508, Mexico
Email: hortensia.reyes@insp.mx

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (10-16)

TCI remifentanil vs. TCI propofol for awake fiber-optic intubation with limited topical anesthesia

Xuyu Zhang¹, Wen He², Xiaodan Wu¹, Xue Zhou¹, Wenqi Huang¹ and Xia Feng¹

¹Department of Anesthesiology, and ²Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
The purpose of this study was to compare the effects of propofol and remifentanil target-controlled infusion (TCI) on awake fiber-optic intubation with limited local anesthesia. 36 patients requiring fiberoptic intubation were randomized to receive propofol (P) or remifentanil (R) effect-site TCI. Target concentrations, sedation levels, pulse oximetry, hemodynamic change, duration, number of adjustments, intubating conditions and recall after surgery were recorded at each stage. The results showed that the target intubation concentration of remifentanil was very close to the sedation concentration but that the intubation concentration of propofol was more than double its sedation concentration (5.83 ± 1.46 μg/ml vs. 2.60 ± 0.47 μg/ml, respectively). Vocal cord opening was significantly better in remifentanil-treated patients. More adjustments and a longer duration were required in propofol-treated patients. Recall was significantly more frequent in remifentanil-treated patients. We concluded that compared to TCI propofol, TCI remifentanil can provide safer and better intubating conditions for fiber-optic intubation with limited local anesthesia.Correspondence to:
X. Feng, MD
Department of Anesthesiology
The First Affiliated Hospital of Sun Yat-Sen University
No 58 zhongshan 2nd RD
Guangzhou, Guangdong, China
Email: fengxiar@sina.com

Abstract

Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase IV inhibitor LC15-0444 and pioglitazone in healthy volunteers

Sung Eun Kim¹, SoJeong Yi¹, Kwang-Hee Shin¹, Tae-Eun Kim¹, Min-Jeong Kim², Youn Hoa Kim³, Seo Hyun Yoon¹, Joo-Youn Cho¹, Sang-Goo Shin¹, In-Jin Jang¹ and Kyung-Sang Yu¹

¹Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, ²Department of Clinical Development and ³Department of DMPK, LG Life Sciences, Ltd, Seoul, Republic of Korea
Objective: LC15-0444, a newly developed selective dipeptidyl peptidase IV inhibitor, has the potential to be administered with other antihyperglycemic agents. The aim of this study was to investigate the interaction between LC15-0444 and pioglitazone by comparing the pharmacokinetics of both compounds and their metabolites. Methods: A randomized, open-label, multiple dosing, three-sequence, three-period, three-treatment crossover study was performed in healthy volunteers. The three treatment groups were comprised of LC15-0444 200 mg, pioglitazone 30 mg, or coadministration of both drugs once daily for 12 days. Blood samples were collected up to 48 hours after the last dosing. Safety and tolerability were assessed throughout the study. Results: The geometric mean ratios (GMRs; (LC15-0444+Pioglitazone coadministered)/(LC15-0444 or Pioglitazone alone)) (90% confidence intervals (CIs)) for C_max,ss and AUC_t,ss of LC15-0444 were 1.06 (0.96 – 1.16) and 0.98 (0.93 – 1.03), respectively. In the case of pioglitazone, the GMRs (90% CIs) for C_max,ss and AUC_t,ss were 0.84 (0.73 – 0.96) and 0.85 (0.76 – 0.96), respectively. All reported adverse events were mild in intensity. Conclusions: The pharmacokinetics of LC15-0444 and its metabolites were not altered by pioglitazone. The systemic exposure of pioglitazone was decreased by 15% after coadministration of LC15-0444 with pioglitazone, but this was not judged to be clinically relevant, considering the total active moiety of pioglitazone.Correspondence to:
K.-S. Yu, MD, PhD
Department of Pharmacology and Clinical Pharmacology
Seoul National University
College of Medicine and Hospital
101 Daehak-ro, Jongno-gu,
Seoul 110-744, Korea
Email: ksyu@snu.ac.kr

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (24-32)

Treatment duration (persistence) of basal insulin supported oral therapy (BOT) in Type-2 diabetic patients: comparison of insulin glargine with NPH insulin

Renate Quinzler¹, Miriam Ude¹,², Alexandra Franzmann¹, Sandra Feldt¹, Katrin Schüssel¹, Kristina Leuner², Walter E. Müller², Franz-Werner Dippel³ and Martin Schulz²,⁴

¹DAPI – German Institute for Drug Use Evaluation, Eschborn, ²Department of Pharmacology, Goethe-University Frankfurt, Frankfurt am Main, ³Sanofi-Aventis Deutschland GmbH and ⁴ABDA – Federal Union of German Associations of Pharmacists, Berlin, Germany
Objective: To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients. Methods: This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006. Results: A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29 – 1.38; unadjusted) and 1.22 (99% CI: 1.18 – 1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results. Conclusion: Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.Correspondence to:
Dr. R. Quinzler
DAPI – German Institute for Drug Use Evaluation
(Verein Deutsches Arzneiprüfungsinstitut e.V.)
Carl-Mannich-Straße 26
65760 Eschborn, Germany

Email: info@dapi.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (33-43)

Pharmacokinetics of single and multiple oral doses of valsartan/amlodipine (80/5 mg) in healthy Chinese subjects

Jingli Duan¹*, Jin Chen²*, Qi Yin³, Rajesh Karan⁴, Karin Meiser⁵, Harold Tom Smith² and Gangadhar Sunkara²

¹Pharmacy Department, Peking University Third Hospital, Beijing, China, ²Translational Sciences, Novartis Institutes for Biomedical Research Inc., East Hanover, NJ, USA, ³Novartis Pharmaceuticals Corporation, Beijing, China, ⁴Novartis Healthcare Pvt. Ltd., Hyderabad, India and ⁵Translational Sciences Biostatistics, Novartis Pharma AG, Basel, Switzerland

*Both authors contributed equally to the manuscript.
Objective: The efficacy and safety of valsartan/amlodipine combination have been demonstrated for the treatment of hypertension. In China, where the prevalence of hypertension is increasing the pharmacokinetic study of valsartan, amlodipine assumes significance. The aim of this study was to characterize the pharmacokinetics (PK) of valsartan and amlodipine following single- and multiple-dose oral administrations of valsartan/ amlodipine 80/5 mg fixed-dose combination in healthy Chinese subjects. Materials and methods: This was an open-label, two-period (single-dose treatment followed by a multipledose (once-daily for 9 days), with a 7-day intertreatment washout period) study conducted in 18 subjects. Serial blood samples were collected at pre-defined time points, and the plasma concentrations of valsartan and amlodipine were measured using LC-MS/MS. Safety was evaluated after single- and multiple-dose drug administration. Results: Following the singledose oral administration of valsartan/amlodipine 80/5 mg, valsartan and amlodipine plasma concentrations reached peak levels at median t_max of 3 and 6 h, respectively. These concentrations declined thereafter, with mean elimination half-lives of 7.7 h (single dose) and 8.6 h (multiple dose) for valsartan, and 47 h (single dose) and 45 h (multiple dose) for amlodipine. After a 9-day multiple-dose treatment (at steady state), accumulation of valsartan and amlodipine was consistent with their half-lives. The single- and multiple-dose administration of valsartan/amlodipine 80/5 mg was associated with asymptomatic hypotension, consistent with the pharmacological activity of the combination of these two blood pressure-lowering drugs when co-administered in healthy subjects. Conclusion: The PK of valsartan and amlodipine are linear following oral administration of valsartan/amlodipine fixed-dose combination.Correspondence to:
Gangadhar Sunkara, PhD
Bldg 438/3407, One Health Plaza
Novartis Pharmaceuticals
East Hanover, NJ 07936,USA
Email: gangadhar.sunkara@novartis.com

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (44-46)

Myelodysplastic syndrome associated with clopidogrel: a case report

Mei Li¹*, Tao Chen¹*, Chun Liang¹, Xixi Xiang², Zhiqing He¹ and Zonggui Wu¹

¹Department of Cardiology, and ²Department of Hematology, the Second Hospital Affiliated to the Second Military Medical University, Shanghai, China

*These authors contributed equally to this work.
More than 3 million patients around the world have received clopidogrel, an inhibitor of platelet aggregation, which has largely replaced ticlopidine in clinical practice as it was believed to be devoid of the side effects caused by ticlopidine. We herein report the case of a woman who developed myelodysplastic syndrome (MDS) after 1 year of treatment with clopidogrel. The absence of other plausible causes suggests that her MDS was induced by clopidogrel. Although this is a very rare case, clinicians should be alert to the possibility of MDS associated with clopidogrel use.Correspondence to:
Z. Wu
Department of Cardiology
The Second Hospital Affiliated to the
Second Military Medical University
Shanghai 200003, China
Email: zgwu@medmail.com

Abstract

Can adenosine cause asthma-like symptoms in patients with cardiac arrhythmias receiving atenolol?

Helena Martinez-Sabater¹, Jesús Cruzado-Quevedo², Luis Muñoz- Gimeno³ and Jesús Hernandez- Cascales¹

¹Department of Pharmacology, Medical School, University of Murcia, Murcia, ²Emergency Department, Hospital Rosell, Cartagena, and ³Emergency Department, Hospital CSV Arrixaca, El Palmar, Murcia, Spain
Correspondence to:
Prof. J. Hernández-Cascales
Departamento de Farmacología
Facultad de Medicina
Campus de Espinardo
30100 Murcia, Spain
Email: jehernca@um.es

Abstract

Can enoxaparin prevent arthrofibrosis?

Mohammad Jafar Emami¹, Hamid Namazi¹, Amir Reza Vosoughi¹, Simin Torabi Nezhad², Ahmad Oryan³ and Kamran Mozaffarian¹

¹Research Center for Bone & Joint Diseases, Chamran Hospital, ²Department of Pathology and Shiraz Nephrology Urology Research Center, Shiraz University of Medical Sciences and ³Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
Correspondence to:
Amir Reza Vosoughi, MD
Chief Resident of Orthopedic Surgery
Research Center for Bone & Joint Diseases
Chamran Hospital
Shiraz University of Medical Sciences
Shiraz, Iran
Email: vosoughiar@hotmail.com

Abstract

Seyffart’s Directory of Drug Dosage in Kidney Disease

F. Keller

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (53-54)

Editorial

Christoph Ritter, Daniel Sehrt and Ulrich Jaehde

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (55-64)

Transbarrier targeting in the intestine: nanomedical options in oncology

Paul Debbage¹ and Gudrun C. Thurner²

¹Department of Anatomy, Histology and Embryology, and ²Department of Radiology, Innsbruck Medical University, Innsbruck, Austria
Correspondence to:
Prof. Dr. phil. Paul Debbage
Medical University Innsbruck
Department of Anatomy
Histology and Embryology
Müllerstraße 59
6020 Innsbruck, Austria
Email: Paul.Debbage@i-med.ac.at

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (65-67)

Androgen receptor and heat shock proteins in progression of prostate cancer cells

Matthias B. Stope¹,², Anne Sauermann¹, Cindy Rönnau², Uwe Zimmermann², Reinhard Walther¹ and Martin Burchardt²

¹Department of Medical Biochemistry and Molecular Biology, and ²Department of Urology, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany
Correspondence to:
Dr. Matthias Stope
Department of Medical Biochemistry and Molecular Biology
Ernst Moritz Arndt University of Greifswald
Fleischmannstraße 42 – 44
17475 Greifswald, Germany
Email: matthias.stope@uni-greifswald.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (68-69)

Ex vivo leukemia models and their potential clinical relevance

Dominik Wolf¹,²

¹University Hospital Bonn, Department of Hematology/Oncology, Bonn, Germany, and ²Internal Medicine V, Hematology and Oncology; Innsbruck Medical University, Innsbruck, Austria
Correspondence to:
Dominik Wolf, MD
Internal Medicine III
University of Bonn, Germany
Email: dominik.wolf@ukb.uni-bonn.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (70-71)

Predictive gene signatures for bevacizumab and cetuximab as well as cytotoxic agents

Heinz-Herbert Fiebig, Vincent Vuaroqueaux, Andre Korrat, Frederic Foucault and Thomas Beckers

Oncotest GmbH, Freiburg, Germany
Correspondence to:
Prof. Dr. Heinz-Herbert Fiebig
Oncotest GmbH
Institute for Experimental Oncology
Am Flughafen 12 – 14
79108 Freiburg, Germany

Email: Fiebig@Oncotest.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (72-73)

Paclitaxel in combination with sorafenib and bevacizumab in patients with locally advanced or metastatic solid tumors

Beate Schultheis, Henrike Neumann, Renée Roy, Vera Heuer, Gerhard Kummer and Dirk Strumberg

Department of Hematology and Oncology, Marienhospital Herne, University of Bochum, Herne, Germany
Correspondence to:
Beate Schultheis, MD
Department of Hematology and Medical Oncology
University of Bochum
Marienhospital Herne
Hölkeskampring 40
44625 Herne, Germany
Email: beate.schultheis@marienhospital-herne.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (74-75)

Angioimmunoblastic T-cell lymphoma, combined with antiphospholipid syndrome and autoimmune thrombocytopenia (Case Report)

Beate Schultheis, Gerhard Kummer, Julian Riebeling and Dirk Strumberg

Department of Hematology and Oncology, Marienhospital Herne, University of Bochum, Herne, Germany
Correspondence to:
Prof. Dr. Dirk Strumberg
Department of Hematology and Oncology
Marienhospital Herne
University of Bochum
Marienhospital Herne
Hölkeskampring 40
44625 Herne, Germany
Email: dirk.strumberg@marienhospital-herne.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (76-78)

Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors

Dirk Strumberg¹, Beate Schultheis¹, Ulrich Traugott², Christiane Vank², Ansgar Santel², Oliver Keil², Klaus Giese², Jörg Kaufmann² and Joachim Drevs³

¹Department of Hematology and Oncology, Marienhospital Herne, University of Bochum, Herne, ²Silence Therapeutics AG, Berlin, and ³Department of Internal Medicine, Gemeinschaftskrankenhaus Herdecke, Herdecke, Germany
Correspondence to:
Prof. Dr. Dirk Strumberg
Department of Hematology and Medical Oncology
Marienhospital Herne
University of Bochum
Hölkeskampring 40
44625 Herne, Germany
Email: dirk.strumberg@marienhospital-herne.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (79-81)

DNA cleavage reactions of the dinuclear chemotherapeutic agent copper(II) bis-1,10- phenanthroline terephthalate

Andrew Kellett¹,², Malachy McCann³, Orla Howe¹, Mark O’Connor¹ and Michael Devereux¹

¹The inorganic pharmaceutical and biomimetic research center, Focas Research Institute, Dublin Institute of Technology, ²School of Chemical Sciences, Dublin City University, Dublin and ³Chemistry Department, National University of Ireland, Maynooth, Ireland
Correspondence to:
Dr. Andrew Kellett
School of Chemical Sciences
Dublin City University
Dublin 9, Ireland
Email: andrew.kellett@dcu.ie

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (82-84)

Variability in fluorouracil exposure during continuous intravenous infusion

Tomi Hendrayana¹,², Verena Kurth¹, Linda Krolop¹, Paul Kenny³, Ralf Axel Hilger⁴, Ingo G.H. Schmidt-Wolf⁵, Yon-Dschun Ko⁶ and Ulrich Jaehde¹

¹Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Germany, ²School of Pharmacy, Institut Teknologi Bandung, Indonesia, ³Saladax Biomedical Inc., Bethlehem, USA, ⁴Department of Internal Medicine, University Hospital of Essen, Essen, ⁵Med. Klinik und Poliklinik III, Center for Integrated Oncology (CIO), University of Bonn, and ⁶Department of Oncology, Internal Medicine, Johanniter Hospital, Bonn, Germany
Correspondence to:
Prof. Dr. Ulrich Jaehde
Institute of Pharmacy
Clinical Pharmacy
University of Bonn
An der Immenburg 4
53121 Bonn, Germany
Email: u.jaehde@uni-bonn.de

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 1/2012 (85-86)

Adaptive randomization procedures for the web-based randomization system RANDI2

Daniel Schrimpf¹ and Lothar R. Pilz²

¹German Cancer Research Center (DKFZ), Department of Biostatistics, Heidelberg and ²University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
Correspondence to:
Daniel Schrimpf
Deutsches Krebsforschungszentrum
Department of Biostatistics
Im Neuenheimer Feld 280
69120 Heidelberg, Germany
Email: d.schrimpf@dkfz.de

Warenkorb Übersicht
Type	Qtty	Price
Der Warenkorb ist leer

Int. Journal of Clinical Pharmacology and Therapeutics Die Online-Versionen der Zeitschriften werden jeweils vor Erscheinen der Print-Ausgabe aktualisiert. Alle Inhalte dieser Website stehen Abonnenten der Zeitschrift nach einmaliger Registrierung ohne Mehrkosten zur Verfügung. Um die Artikel im PDF-Format betrachten zu können, benötigen Sie die Adobe Reader® Software.
Preis für gesamte Ausgabe: 30.00$

Benutzername:
Passwort:

Volume 50, No. 1/2012(January)