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The role of Pharmacometrics in the development of Cuban Biotechnology products

Abstract:

Pharmacometrics is a vibrant scientific discipline that involves a cycle of excellence: integration, innovation and impact. This work was aimed to assess different pharmacometric approaches in three Cuban biotechnological products. A population pharmacokinetic analysis of nimotuzumab was performed in patients with stage III breast cancer with different doses of it, in combination with doxorubicin and cyclophosphamide. The pharmacokinetic/pharmacodynamic (PK/PD) characterization of Pegylated Recombinant Human Erythropoietin (rHuEPO) branched 32 kDa-PEG-rHuEPO and 40 kDa- PEG-rHuEPO was conducted and compared with reference products (ior®EPOCIM and MIRCERA®) in New Zealand rabbits. Data were analyzed using the nonlinear mixed–effect approach (NONMEM®). The best model for nimotuzumab was the Quasi Steady State approximation of the full Target Mediated Drug Disposition model that best described the linear and nonlinear PK. The recommended optimal biological dose ranged between 200-400mg/ week. On the other hand, a cell transit semi-mechanistic PK/PD model for characterizing rHuEPO profiles was obtained. The development of new branched PEG-chain formulations of rHuEPO improves its PK and PD properties, compared to those of commercially available formulations (i.e., ior®EPOCIM and MIRCERA®). Due to its integrative nature and pbkp_redictive value, population modeling was very useful in the optimal characterization of the pharmacokinetic and pharmacodynamic properties of these three Cuban biotech drug products. It had a significant impact on decision-making by both the national regulatory agency and the local biopharmaceutical industry as to their research and development plans, as well as the subsequent marketing strategies for these new products, with substantial economic and time saving benefits. This work received the Annual Award of the Cuban Academy of Sciences for the year 2019.