RESUMO
Marketed formulations of erythropoietin (EPO) ior®EPOCIM, MIRCERA® and two newly developed pegylated-EPO analogues (PEG-EPO 32 and 40â¯kDa) formulations were intravenously administered to New Zealand rabbits. A semi-mechanistic Pharmacokinetic/Pharmacodynamic (PK/PD) model describing in a simultaneous and integrated form the time course of reticulocytes, red blood cells and hemoglobin was built to account for the time course of hematopoiesis stimulation after erythropoietin administration. Data analysis was performed based on the population approach with the software NONMEM version 7.3. Erythropoietin disposition of each of the administered formulations was best described with a two compartment model and linear elimination. Different formulations show different clearance and apparent volume of distribution of the central compartment but share estimates of inter-compartmental clearance and apparent peripheral volume of distribution. A semi-mechanistic model including cell proliferation, maturation, and homeostatic regulation provided a good description of the data regardless the type of erythropoietin formulation administered. The system-, and drug-related parameters showed consistency and differed across formulations, respectively. A single IV administration of PEG-EPO 32 and 40â¯kDa formulations in New Zealand rabbits achieves a median change of 27% and 22% on RET levels, and of 47% and 63% on RBC and HGB levels, respectively compared to MIRCERA®. The administration of new branched PEG-chains formulations improves PK and PD properties of EPO, in terms of increasing elimination half-lives and pharmacological activity on RET, RBC and HGB compared to commercially available formulations (ior®EPOCIM and MIRCERA®).
Assuntos
Eritropoetina/farmacocinética , Hematínicos/farmacocinética , Hematopoese/efeitos dos fármacos , Modelos Biológicos , Polietilenoglicóis/farmacocinética , Animais , Disponibilidade Biológica , Composição de Medicamentos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritropoetina/administração & dosagem , Eritropoetina/sangue , Eritropoetina/química , Hematínicos/administração & dosagem , Hematínicos/sangue , Hematínicos/química , Hemoglobinas/metabolismo , Injeções Intravenosas , Modelos Lineares , Masculino , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Coelhos , Proteínas Recombinantes/farmacocinética , Reticulócitos/efeitos dos fármacos , Reticulócitos/metabolismoRESUMO
Para valorar la eficacia y seguridad del enclavado endomedular fresado se hace un estudio retrospectivo de 74 casos de fracturas abiertas de la diáfisis de tibia tratados mediante esta técnica con un seguimiento mínimo de 1 año. Basados en la clasificación de Gustilo, 45 casos eran Grado I, 25 Grado II y cuatro Grado IIIA.La demora media en el enclavado fue de 9 días. Todas las fracturas consolidaron en un tiempo medio de 4 meses.En ningún caso se realizó aporte de injerto óseo. Las complicaciones encontradas fueron infección en el 4 por ciento, dismetría mayor de 1 cm en un caso, rotura de un tornillo en un caso y angulación entre 5 y 10° de valgo en 13 casos. Los resultados sugieren que el enclavado endomedular fresado es una opción segura y eficaz para el tratamiento de las fracturas abiertas de la diáfisis tibial Grados I, II y IIIA (AU)