Physiologically based pharmacokinetic modelling to inform combination dosing regimens of ceftaroline and daptomycin in special populations.

AIMS: The combination of daptomycin and ceftaroline used as salvage therapy is associated with higher survival and decreased clinical failure in complicated methicillin-resistant Staphylococcus aureus (MRSA) infections that are resistant to standard MRSA treatment. This study aimed to evaluate dosing regimens for coadministration of daptomycin and ceftaroline in special populations including paediatrics, renally impaired (RI), obese and geriatrics that generate sufficient coverage against daptomycin-resistant MRSA. METHODS: Physiologically based pharmacokinetic models were developed from pharmacokinetic studies of healthy adults, geriatric, paediatric, obese and RI patients. The predicted profiles were used to evaluate joint probability of target attainment (PTA), as well as tissue-to-plasma ratios. RESULTS: The adult dosing regimens of 6 mg/kg every (q)24h or q48h daptomycin and 300-600 mg q12h ceftaroline fosamil by RI categories achieved ≥90% joint PTA when the minimum inhibitory concentrations in the combination are at or below 1 and 4 µg/mL against MRSA. In paediatrics, wherein there is no recommended daptomycin dosing regimen for S. aureus bacteraemia, ≥90% joint PTA is achieved when the minimum inhibitory concentrations in the combination are up to 0.5 and 2 µg/mL for standard paediatric dosing regimens of 7 mg/kg q24h daptomycin and 12 mg/kg q8h ceftaroline fosamil. Model predicted tissue-to-plasma ratios of 0.3 and 0.7 in the skin and lung, respectively, for ceftaroline and 0.8 in the skin for daptomycin. CONCLUSION: Our work illustrates how physiologically based pharmacokinetic modelling can inform appropriate dosing of adult and paediatric patients and thereby enable prediction of target attainment in the patients during multitherapies.

A regulação sanitária brasileira e a Hemobrás / Brazilian sanitary regulation and Hemobrás

A Hemobrás é uma empresa criada para possibilitar o acesso, pela população,aos medicamentos produzidos a partir do plasma humano e oriundos de processos biotecnológicos. Todo o ciclo produtivo de tais medicamentos é regulado por legislações sanitárias, as quais serão apresentadas e discutidas neste trabalho. Observamos que muitas destas normas são antigas e precisam de reformulação para atender melhor o grande avanço dos últimos anos nesta área, pois não condizem mais com o novo cenário brasileiro e mundial. Além disso, a Hemobrás tem exercido um papel relevante para o amadurecimento e o progresso das normas que regulamentam o setor de medicamentos no Brasil.

The Hemobrás is a company created to facilitate access by the population to medicines made from human plasma and derived from biotechnological processes. Throughout the production cycle of these drugs is regulated by sanitary laws, which were presented and discussed in this paper. We note that many of these standards are old and need reshaping to better meet the great advance in recent years in this area, because more do not fit with the new Brazilian and global scenario. Furthermore, Hemobrás has played an important role for the maturation and advancement of standards governing the drug industry in Brazil.