[Speaker] Leyanis Rodriguez Vera:1
[Co-author] Niurys De Castro-Suarez:1, Carlos Villegas:2, Jose M. Davalos:3, Raymed Bacallao:3, Patricia Luaces:4, Mayra Ramos Suzarte:4
1:Pharmacy Department, Institute of Food and Pharmacy, University of Havana, Cuba, 2:National Institute of Radiobiology and Oncology (INOR), Havana, Cuba, 3:National Institute of Nephrology, Havana, Cuba, 4:Center of Molecular Immunology (CIM), Havana, Cuba

Autosomal dominant polycystic kidney disease is a common genetic disease characterized by an overexpression and mislocalization of epidermal growth factor receptor (EGFR) to the apical membranes of cystic epithelial cells. The nimotuzumab® is a genetically engineered humanized antibody developed at the Center of Molecular Immunology (Havana, Cuba). Nimotuzumab blocks EGFR-ligand interactions and subsequent signal transduction events. A Phase I, single center, and non-controlled open clinical study was carried out. Five patients were enrolled at each of the following fixed dose levels: 50, 100, 200 and 400 mg. Blood samples were drawn during 28 days for pharmacokinetic assessments. Subjects were closely monitored during the trial and once finished the administration of nimotuzumab, including the anti-idiotypic response. This study was conducted in compliance with the regulations of the Declaration of Helsinki regarding the ethical use of human subjects in clinical trials. For the first time, the nimotuzumab was used for treating a non-oncological disease and the duration of pharmacokinetic sampling was considerably longer (up to 28th day) than other pharmacokinetics studies of anti-EGFR mAb. The administration of nimotuzumab showed dose-dependent kinetics. Nimotuzumab does not develop anti-idiotypic response against the murine portion present in the hypervariable region of the antibody present in the serum of the patients treated. No significant differences were found in the systemic clearance between the 100 and 400 mg dose, which indicates that the optimal biological dose is in this range of dose. These results that are shown in this investigation constitute the preliminary bases for the future population pharmacokinetic analyses of this mAb.
Acknowledged: This research was possible with the special contribution to the Collaboration Projects between the Center of Molecular Immunology and Institute of Food and Pharmacy, University of Havana. Cuba.

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