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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
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
Renata Rezonja Kukec, Iztok Grabnar, Tomaz Vovk, Ales Mrhar, Viljem Kovac and Tanja Cufer
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.
Patrick M. Honore, Rita Jacobs, Olivier Joannes-Boyau, Willem Boer, Elisabeth De Waele, Viola Van Gorp and Herbert D. Spapen
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4. Yahav D
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Nina Erculj, Barbara Faganel Kotnik, Marusa Debeljak, Janez Jazbec and Vita Dolzan
. Association of genetic polymorphism in the folate metabolic pathway with methotrexate pharmacokinetics and toxicity in childhood acute lymphoblastic leukaemia and malignant lymphoma. Eur J Clin Pharmacol 2011; 67: 993-1006.
4. Erculj N, Kotnik BF, Debeljak M, Jazbec J, Dolzan V. Influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in childhood acute lymphoblastic leukemia. Leuk Lymphoma 2012; 53: 1096-104.
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Ayman Geddawy, Yasmine F. Ibrahim, Nabil M. Elbahie and Mohammad A. Ibrahim
approved in combination with PegIFN-alpha and ribavirin for the treatment of chronic HCV genotype 1 infection in 2011.  However, these drugs have been reported to have several drug-drug interactions, and are largely replaced with newer DAA including Simeprevir, Paritaprevir, Daclatasvir, Ledipasvir, Ombitasvir, Sofosbuvir and Dasabuvir. Table 3 summarizes the pharmacokinetics of all approved DAA with special reference to the sites of drug-drug interaction. Clinical pharmacology of the newer DAA will be discussed in the next section.
Maria-Magdalena Leon-Constantin, Alexandra Maștaleru, Ovidiu Mitu, Madalina Zota, Teodor Vasilcu, Radu Gavril and Florin Mitu
, pharmacokinetics and pharmacodynamics, and safety and efficacy in phase 1 subjects. AmJ Emerg Med. 2016;34(11S):26-32.
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