Abstract
To evaluate the modification of pharmacodynamic parameters induced by the administration of l-asparaginase loaded into red blood cells, 13 patients received a single dose of l-asparaginase internalised into the carrier. The enzyme was loaded using a reversible lysis-resealing process. The dose per patient ranged from 30 to 200 IU·kg−1. Considerable heterogeneity occurred between patients: the level of l-asparaginase circulating after 24 h represented 47% of the total injected dose as compared to 74.8% for red blood cells (RBCs). However, the half-life of the enzyme remaining in the circulation was very similar to that of the RBC carrier, i.e. 29 days and 27 days, respectively, compared with 8–24 h for the free enzyme. Sustained elimination of plasma l-asparagine occurred, the duration of which was dependent on the injected dose. A single injection of 30·IU·kg−1 was sufficient to eliminate plasma l-asparagine over 10 days. With 150–200 IU·kg−1 the elimination period was extended to 50 days. These data show that the use of RBCs as carriers of l-asparaginase greatly improves the pharmacodynamic parameters of the drug.
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Kravtzoff, R., Ropars, C., Desbois, I. et al. Improved pharmacodynamics of l-asparaginase-loaded in human red blood cells. Eur J Clin Pharmacol 49, 465–470 (1996). https://doi.org/10.1007/BF00195932
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DOI: https://doi.org/10.1007/BF00195932