Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ Preparations in Patients with Severe Hemophilia A / 中国实验血液学杂志

OBJECTIVE@#To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients.@*METHODS@#A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated.@*RESULTS@#The median age of 42 patients with severe hemophilia A was 31（16-50） years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05).@*CONCLUSION@#Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.

Drugs obtained by biotechnology processing / Drogas obtidas pelo processamento biotecnológico

In recent years, the number of drugs of biotechnological origin available for many different diseases has increased exponentially, including different types of cancer, diabetes mellitus, infectious diseases (e.g. AIDS Virus / HIV) as well as cardiovascular, neurological, respiratory, and autoimmune diseases, among others. The pharmaceutical industry has used different technologies to obtain new and promising active ingredients, as exemplified by the fermentation technique, recombinant DNA technique and the hybridoma technique. The expiry of the patents of the first drugs of biotechnological origin and the consequent emergence of biosimilar products, have posed various questions to health authorities worldwide regarding the definition, framework, and requirements for authorization to market such products.

Nos últimos anos, tem aumentado exponencialmente o número de fármacos de origem biotecnológica ao dispor das mais diversas patologias, entre elas destacam-se, os diferentes tipos de cancêr, as doenças infecciosas (ex. vírus AIDS/HIV), as doenças autoimunes, as doenças cardiovasculares, a Diabetes Mellitus, as doenças neurológicas, as doenças respiratórias, entre outras. A indústria farmacêutica tem recorrido a diferentes tecnologias para a obtenção de novos e promissores princípios ativos, como são exemplo a fermentação, a técnica de DNA Recombinante, a técnica de hidridoma, entre outras. A queda das patentes dos primeiros fármacos de origem biotecnológica e o consequente aparecimento dos produtos biossimilares têm colocado diferentes questões às autoridades de saúde mundiais, sobre a definição, enquadramento e exigências para a autorização de entrada no mercado deste tipo de produtos.

Estudio densitométrico del tejido óseo neoformado por el uso de rhBMP-2 en mandíbulas de ratas Wistar / Optical densitometry study of the newly formed bone using rhBMP-2 in Wistar rat mandibles

The purpose of this study was to evaluate the efficacy of monoolein gel as a carrier for rhBMP-2 in the healing bone process of critical bone defects created in Wistar rats mandibles using digitalized radiographic method to analyze this process. In the group 1, the rhBMP-2 was dissolved in aqueous solution and in the group 2, the rhBMP-2 was combined with monoolein gel as a carrier. The results showed that in both of groups it was found efficient bone repair, with a great optical density in the group that the rhBMP-2 was combined with the monoolein gel, but without statistical difference between them.

El objetivo de este estudio fue evaluar la eficiencia del gel de monoolein como portador de la rhBMP-2 en el proceso de recuperación de la osificación en defectos osteos creados en mandíbulas de ratos Wistar, por medio de radiografias digitalizadas como método de análisis. En el grupo 1, la rhBMP-2 fue disuelta en solución acuosa y en el grupo 2, la rhBMP-2 fue combinada al gel de monoolein como portador. Los resultados mostraron que los dos grupos presentaron un eficiente reparo osteo, con mayor densidad óptica en el grupo en que la rhBMP-2 fue combinada con el gel de monoolein, pero sin diferencia estadística significante entre ellos.

Recombinant human granulocyte-macrophage colony-stimulating factor: effect of glycosylation on pharmacokinetic parameters

The pharmacokinetic behaviour of the non-glycosylated, bacterially-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and the glycosylated mammalian product was studied after intra and extra vascular administration of a single dose in rodents. Each route of administration gave a different rhGM-CSF concentration-time profile. After extra vascular administration of equivalent doses, a higher peak concentration and faster elimination were observed in the group treated with the E. coli-derived cytokine. The faster elimination resulted in a return to pre-treatment plasma levels after 12 hrs, versus 48 hrs following the administration of glycosylated rhGM-CSF. After intravascular administration, clearance of rhGM-CSF was significantly decreased by the presence of carbohydrates. Non-significant differences in the terminal phase of the biphasic kinetics were found, but the distribution phase was significantly longer for the glycosylated form