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Metastatic Renal Cell Carcinoma: Sunitinib as First-Line Treatment; Results of a Retrospective Study

and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther. 2003; 2:471-8. [15] Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003; 9:327-37. [16] Pantuck AJ, Zeng G, Belldegrun AS, Figlin RA. Pathobiology, prognosis and targeted

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Efficacy and Tolerability of Eight Antimicrobial Regimens in the Outpatient Treatment of Exacerbations of Chronic Obstructive Pulmonary Disease

outpatient acute exacerbations of COPD: MAESTRAL results. Eur Respir J. 2012;40(1):17-27. 31. Siempos II, Dimopoulos G, Korbila JP, Manta K, Falagas ME. Macrolides, quinolones and amoxicillin/clavulonate for chronic bronchitis: meta-analysis. Eur Respir J. 2007; 29 (6): 1127-1137. 32. Perry CM, Brogden RN. Cefuroxime Axetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1996; 52 (1): 125-156. 33. Destache CJ, Dewan N, O’Donohue WJ, Campbell JC, Anqelillo VA. Clinical and

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Qualitative Histological Analysis of Adrenal Cortex Following Application of Medroxyprogesterone Acetate

medroxyprogesterone acetate on the pituitary-adrenal axis. J Clin Endocrinol Metab. 1976;42(5):912-7. doi:10.1210/jcem-42-5-912 PMID:178684. Blossey HC, Wander HE, Koebberling J, Nagel GA. Pharmacokinetic and pharmacodynamic basis for the treatment of metastatic breast cancer with high-dose medroxyprogesterone acetate. Cancer. 1984;54(6 Suppl):1208-15. doi:10.1002/1097-0142(19840915)54:1+<1208::AID-CNCR2820541319>3.0.CO;2-K PMID:6088020. van Veelen H, Willemse PH, Sleijfer DT, van der Ploeg E, Sluiter WJ, Doorenbos H. Mechanism

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Potential Effects of Bee Honey and Propolis Against the Toxicity of Ochratoxin A in Rats

. Effect of a necrogenic dose of diethylnitrosamine on vitamin E-deficient and vitamin E-supplemented rats. Food Chem Toxicol. 1998;36(11):929-35. doi:10.1016/S0278-6915(98)00043-X PMID:9771554 Rowland M, Tozer TN. In Clinical Pharmacokinetics: Concepts and Applications, 3 rd ed. Lea, Febiger: Philadelphia , 1989:148-160. Gheldof N, Engeseth NJ. Antioxidant capacity of honey from various floral sources based on the determination of oxygen radical absorbance capacity and inhibition of lipoprotein oxidation in human

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Distribution of CYP2C9 and VKORC1 Gene Polymorphisms in Healthy Macedonian Male Population

genotypes and the pharmacokinetics of tenoxicam in Brazilians. Clin Pharmacol Ther. 2004; 76(1):18-26. 21. Dandara C, Lombard Z, Du Plooy I, McLellan T, Norris SA, Ramsay M. Genetic variants in CYP (-1A2, -2C9, -2C19, -3A4 and -3A5), VKORC1 and ABCB1 genes in a black South African population: a window into diversity.Pharmacogenomics. 2011; 12 (12):1663-70. 22. Hamdy SI, Hiratsuka M, Narahara K, El-Enany M, Moursi N, Ahmed MS, Mizugaki M. Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and

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Apnea in preterm newborns: determinants, pathophysiology, effects on cardiovascular parameters and treatment

Respiratory Care. Springer Sience + Business Media, LLC 2012., p.251-252. ISBN:987-1-4614-2154-2. 59. Dobson NR, Hunt CE. Pharmacology review: Caffeine use in neonates: Indications, pharmacokinetics, clinical effects, outcomes. Neoreviews, 2013; 14: e540-e550. 60. Aranda JV, Beharry K, Valencia GB, Natarajan G, Davis J. Caffeine impact on neonatal morbidities. The Journal of Maternal-Fetal and Neonatal Medicine, 2010; 23(S3): 20-23. 61. Patel RM, Leong T, Carlton P, Vyas-Read S. Early caffeine therapy and clinical outcomes

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Cannabis and alcohol in road traffic: an overview

. Developing limits for driving under cannabis. Addiction 2007; 102: 1910–7. 23. Berghaus G, Sticht G, Grellner E, Lenz D, Naumann T, Wiesenmüller S. Meta analysis of empirical studies concerning the effects of medicines and illegal drugs including pharmacokinetics on safe driving. DRUID Deliverable D 1.1.2b. Würzburg, Germany: University of Würzburg; 2010. 24. Kelly E, Darke S, Ross J. A review of drug use and driving: epidemiology, impairment, risk factors and risk perceptions. Drug Alcohol Rev 2004; 23: 319–344. 25. Berghaus G, Sheer N, Schmidt P

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Biosimilar medicines and patient registries – expectations, limitations, and opportunities

Conference Paper: Annual European Congress of Rheumatology , 2017. 42. Kim W, Buske C, Oqura M, Jurczak W, Sancho J, Zhavrid E, Kim J, Hernandez-Rivas J, Prokharau A, Vasilica M, Nagarkar R, Osmanov D, Kwak L, Lee S, Lee S, Bae Y, Coiffier B. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol 2017; 4(8): e362-e373. doi: 10.1016/S2352-3026(17)30120-5. Epub 2017 Jul 14

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Therapeutic Drug Monitoring in Rheumatic Diseases

1 Introduction The main goal of treating rheumatic diseases is to achieve rapid and effective suppression of inflammation. More and more drugs have been proven to be able to achieve these goals nowadays. The current practice is to give a recommended dose of drugs to our patients according to the body weight, risk factors and tolerance, etc. However, all our patients are different individuals who have different pharmacokinetics, and this difference in pharmacokinetics can affect the true drug concentration that is working inside them. This may create

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Febrile neutropenia in chemotherapy treated small-cell lung cancer patients


Background. Chemotherapy with platinum agent and etoposide for small-cell lung cancer (SCLC) is supposed to be associated with intermediate risk (10-20%) of febrile neutropenia. Primary prophylaxis with granulocyte colonystimulating factors (G-CSFs) is not routinely recommended by the treatment guidelines. However, in clinical practice febrile neutropenia is often observed with standard etoposide/platinum regimen. The aim of this analysis was to evaluate the frequency of neutropenia and febrile neutropenia in advanced SCLC patients in the first cycle of standard chemotherapy. Furthermore, we explored the association between severe neutropenia and etoposide peak plasma levels in the same patients.

Methods. The case series based analysis of 17 patients with advanced SCLC treated with standard platinum/etoposide chemotherapy, already included in the pharmacokinetics study with etoposide, was performed. Grade 3/4 neutropenia and febrile neutropenia, observed after the first cycle are reported. The neutrophil counts were determined on day one of the second cycle unless symptoms potentially related to neutropenia occurred. Adverse events were classified according to Common Toxicity Criteria 4.0. Additionally, association between severe neutropenia and etoposide peak plasma concentrations, which were measured in the scope of pharmacokinetic study, was explored.

Results. Two out of 17 patients received primary GCS-F prophylaxis. In 15 patient who did not receive primary prophylaxis the rates of both grade 3/4 neutropenia and febrile neutropenia were high (8/15 (53.3%) and 2/15 (13.3%), respectively), already in the first cycle of chemotherapy. One patient died due to febrile neutropenia related pneumonia. Neutropenic events are assumed to be related to increased etoposide plasma concentrations after a standard etoposide and cisplatin dose. While the mean etoposide peak plasma concentration in the first cycle of chemotherapy was 17.6 mg/l, the highest levels of 27.07 and 27.49 mg/l were determined in two patients with febrile neutropenia.

Conclusions. Our study indicates that there is a need to reduce the risk of neutropenic events in chemotherapy treated advanced SCLC, starting in the first cycle. Mandatory use of primary G-CSF prophylaxis might be considered. Alternatively, use of improved risk models for identification of patients with increased risk for neutropenia and individualization of primary prophylaxis based on not only clinical characteristics but also on etoposide plasma concentration measurement, could be a new, promising options that deserves further evaluation.

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