Volume 42, No. 11/2004(November)
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 Int. Journal of Clinical Pharmacology and Therapeutics
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Drug Utilization
Off-label use of proton pump inhibitors and b-blockers in general practices: an analysis using the Disease Analyzer – mediplus patient database
Abstract
D. Schröder-Bernhardi, K. Roth and G. Dietlein
IMS HEALTH, Frankfurt am Main, Germany
Objective: The off-label use of medicines is a widespread phenomenon in medical practice but discussion on the legality of using drugs outside their licensed indications is still ongoing. Prescription recommendations and prescribing habits can differ greatly. We have used a database tool to analyze replies to a batch of questions which included the question “Is the off-label use of medications common?”. Methods: The analysis was carried out using the Disease Analyzer – mediplus patient database, which is a database tool registered in Germany. It enabled the anonymous access to a representative panel of physicians and patients. More than 1,500 medical practices representing approximately 2.5 million patients were analyzed in a cross-sectional or longitudinal manner. The Disease Analyzer – mediplus database is unique in that it has direct links to individual diagnoses and the corresponding therapy. Results: The findings demonstrated that proton pump inhibitors (PPI), which are licensed for the treatment of gastric ulcer and gastric reflux, are also used off-label in gastritis. The off-label use varies from 30 – 40% of prescriptions. The data indicate that the prescribing behavior has been influenced by the ending of the patent protection on omeprazole. A second instance which has been identified involves the b-blocker carvedilol, which is licensed for the treatment of heart failure (24% of the total number of patients receiving the drug) but it was found that other b-blockers are used off-label in this indication at a rate of more than 10% of prescriptions. Conclusion: The off-label use of drugs is high, especially in gastritis and heart failure. The investigation has also confirmed that the Disease Analyzer – mediplus database provides quantitative and qualitative analyses combining all relevant information concerning physicians, patients, diagnoses and therapy and that this information can be used to evaluate prescribing habits and trends with regard to the off-label use of drugs.Correspondence to:
Dr. G. Dietlein
IMS HEALTH
Hahnstraße 30 – 32
60528 Frankfurt/Main, Germany
Email: gerharddietlein@web.de
Pharmacodynamics
Effect of monthly atorvastatin treatment on hemostasis
Abstract
B. Okopien, R. Krysiak and Z.S. Herman
Department of Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
Apart from lowering lipid levels, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) produce many other favorable effects that contribute to their clinical efficacy in the primary and secondary prevention of cardiovascular diseases. The aim of this study was to assess the effect of 30-day atorvastatin treatment on major hemostatic risk factors (fibrinogen, PAI-1 levels, factor VII coagulant activity) in patients with primary hypercholesterolemia. We studied 18 hypercholesterolemic patients and 12 matched control subjects. Compared to the control subjects, hypercholesterolemic patients exhibited increased plasma PAI-1 levels and factor VII activity. Atorvastatin (20 mg/d) not only decreased total cholesterol, LDL cholesterol and oxidized LDL, but also reduced PAI-1 levels and factor VII activity and tended to decrease fibrinogen levels. The hemostatic effects of atorvastatin did not correlate with its lipid-lowering potential. Our study is the first to show that atorvastatin may exhibit a quick, beneficial and multidirectional nonlipid-related effect on hemostasis.Correspondence to:
Dr. R. Krysiak
Department of Clinical Pharmacology
Medical University of Silesia
Medyków 18
40-752 Katowice, Poland
Email: r.krysiak@pharmanet.com.pl
Pharmacotherapy
Treatment of gastric hemorrhage by pulverized omeprazole and antacid – concomitant administration via a nasogastric tube
Abstract
T. Yamaguchi, S. Mukai, E. Kinoshita, H. Ohtani and Y. Sawada
1Department of Hospital Pharmacy, 2Pediatrics, Isahaya Ryoiku Center, Nagasaki, and 3Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka Japan
Gastroesophageal reflux (GER) is a common episode in pediatric patients with severe motor and intellectual disabilities (SMID) and occasionally leads to a severe clinical state accompanied with nausea, hematemesis, melena, wheezing, pneumonia, anemia and/or failure to thrive. We report here a case of a 14-year-old male with Lennox syndrome who had been treated with a histamine H2 blocker intravenously or via a nasogastric tube for repeated gastric hemorrhage due to severe GER. Since his gastric hemorrhage became resistant to the H2 blocker, we decided to replace it with a proton pump inhibitor (PPI). Although lansoprazole can be decapsulated for administration via a nasogastric tube, it tends to block fine tubes. The acid-sensitive drug omeprazole, another oral PPI, is commercially available as enteric-coated tablets. Therefore, we pulverized the tablets and administered omeprazole, mixed with a small amount of antacid, via a nasogastric tube. The patient’s gastric hemorrhage was dramatically improved. Thus, administration of pulverized omeprazole concomitantly with antacid via a fine nasogastric tube may provide a novel approach for the treatment of chronic GER in pediatric patients with SMID.Correspondence to:
T. Yamaguchi
Department of Hospital Pharmacy
Isahaya Ryoiku Center
537-24 Uki-machi, Isahaya, Nagasaki 854-0121, Japan
Email: gzw05275@nifty.com
Bioavailability Section
Comparative bioavailability of a novel timed release and powder-filled glucosamine sulfate formulation – a multi-dose, randomized, crossover study
Abstract
M. Basak, S. Joseph, S. Joshi and S. Sawant
1Pharma Base India Pvt. Ltd., T.P.S. III, Bandra (W), Mumbai, and
2Accutest Research Laboratories Pvt. Ltd., Koper Khairane, Navi Mumbai, India
Objective: The absorption of 2 different formulations of glucosamine sulfate were studied in a randomized, multi-dose, two-way, crossover study. Materials and method: In this study, a novel timed release pellet-filled hard gelatin shell capsule (TimeOsamine™) was compared with a powder-filled hard gelatin shell capsule. The timed release capsule was used in a double dose with an interval of 12 h whereas the powder-filled hard gelatin capsule was used in a triple dose schedule with an interval of 8 h after 10 h pre-dose fasting. Twelve healthy male subjects were administered a 1,000 mg (2 × 500 mg) dose of timed release glucosamine sulfate (TimeOsamine™) or a 1,500 mg (3 × 500 mg) dose of the powder-filled glucosamine sulfate formulation. The concentration of glucosamine was measured over the next 24 h. Pharmacokinetics properties including area under the curve (AUC), maximum concentration in plasma (Cmax), time to maximum plasma concentration (tmax) were measured. Results: The Cmax of the powder-filled and timed release formulation (TimeOsamine™) was 543.12 ng/ml and 520.98 ng/ml, respectively. The tmax of TimeOsamine™ was delayed by 4.13 h, whereas the powder-filled preparation was 1.00 h. The AUC0-24 of the 2 doses of TimeOsamine™ (2 ´ 500 mg = 1,000 mg) and the 3 doses of the powder-filled formulation (3 ´ 500 mg = 1,500 mg) was 6,263.32 ng ´ h/ml and 6,499.55 ng ´ h/ml, respectively. Conclusion: After reduction in the dose by 33%, the AUC0-24 of TimeOsamine™ is 96.37% with respect to the powder-filled formulation AUC0-24, which is comparable. Correspondence to:
M. Basak, PhD
Pharma Base India Pvt. Ltd., T.P.S. III, Bandra (W)
201/D – Triveni Building
32nd Street
Mumbai – 400 050, India
Email: pbindia@bom5.vsnl.net.in
Abstracts
Extended Abstracts
Annual Meeting of the Working Group for Pharmacology in Oncology and Hematology (APOH) of the Central European Society for Anticancer Drug Research – EWIV (CESAR)
Extended Abstracts
Differential protein expression pattern in tamoxifen-sensitive and -resistant breast cancer xenografts
Abstract
I. Fichtner, M. Becker, V. Besada and L. Castellanos-Serra
Extended Abstracts
Proteome analysis of renal cell carcinoma to develop new strategies in diagnosis and therapy
Abstract
R. Walther, S. Balabanov, H. Junker, C. Scharf and U. Zimmermann
Extended Abstracts
Differential gene expression studies in cisplatin-sensitive versus cisplatin-resistant human cancer cell lines
Abstract
E.M. Gosepath, S. Weykam, E. Gruenewald, Y. Ko, M. Wiese and M.U. Kassack
Extended Abstracts
Influence of doxorubicin on gene expression and protein pattern in HeLa cells
Abstract
S. Bien, C.A. Ritter, M. Kranz, C. Scharf, L. Steil, M. Hummel, U. Völker, I. Cascorbi and H.K. Kroemer
Extended Abstracts
Mechanisms of resistance development against trastuzumab (Herceptin) in an in vivo breast cancer model
Abstract
C.A. Ritter, R. Bianco, T. Dugger, J. Forbes, S. Qu, C. Rinehart, W. King and C.L. Arteaga
Extended Abstracts
Novel modulators to overcome P-glycoprotein-mediated multidrug resistance in tumor cells
Abstract
H. Müller, W. Klinkhammer, M.U. Kassack, N. Eckstein and M. Wiese
Extended Abstracts
Reactivity of novel albumin-binding platinum complexes
Abstract
D. Garmann, A. Warnecke, F. Kratz and U. Jaehde
Extended Abstracts
Correlation of ERK-phosphorylation and toxicities in patients treated with the Raf kinase inhibitor BAY 43-9006
Abstract
R.A. Hilger, S. Kredtke, M.E. Scheulen, S. Seeber and D. Strumberg
Extended Abstracts
Results of a phase I trial of BAY 43-9006 in combination with doxorubicin in patients with primary hepatic cancer
Abstract
H. Richly, P. Kupsch, K. Passage, M. Grubert, R.A. Hilger, R. Voigtmann, B. Schwartz, E. Brendel, O. Christensen, C.G. Haase and D. Strumberg
Extended Abstracts
Metronomic scheduling of trofosfamide chemotherapy in human NSCLC xenografts highly increases therapeutic efficacy compared to conventional scheduling by inhibition of angiogenesis
Abstract
S. Stölting, T. Klink, C. Bela, C. Engels and T. Wagner
Extended Abstracts
Pharmacokinetics of treosulfan in a myeloablative combination with cyclophosphamide prior to allogeneic hematopoietic stem cell transplantation
Abstract
R.A. Hilger, J. Baumgart, M.E. Scheulen, R. Trenschel, D. Strumberg, S. Seeber and D.W. Beelen
Extended Abstracts
Novel indirubin derivatives, promising anti-tumor agents
inhibiting cyclin-dependent kinases
Abstract
K.-H. Merz, S. Schwahn, F. Hippe, S. Mühlbeyer, S. Jakobs and G. Eisenbrand
Extended Abstracts
mproved viability of human tumor samples in a new oxygen-enriched solution
Abstract
M. Heim, R.A. Hilger, S. Kredtke, D. Thyssen, F. Bach and D. Strumberg
Extended Abstracts
Treosulfan based conditioning for autologous and allogeneic hematopoietic stem cell transplantation
Abstract
J. Casper and M. Freund
