IMPROVED PHARMACODYNAMICS OF L-ASPARAGINASE LOADED IN HUMAN RED-BLOOD-CELLS

To evaluate the modification of pharmacodynamic parameters induced by the administration of L-asparaginase loaded into red blood cells, 13 p atients received a single dose of L-asparaginase internalised into the carrier. The enzyme was loaded using a reversible lysis-resealing pro cess. The dose per patient ranged from 30 to 200 IU . kg(-1). Consider able heterogeneity occurred between patients: the level of L-asparagin ase circulating after 24 h represented 47% of the total injected dose as compared to 74.8% for red blood cells (RBCs). However, the half-lif e 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 w ith 8-24 h for the free enzyme. Sustained elimination of plasma L-aspa ragine occurred, the duration of which was dependent on the injected d ose. A single injection of 30 . IU . kg(-1) was sufficient to eliminat e plasma L-asparagine over 10 days. With 150-200 IU . kg(-1) the elimi nation period was extended to 50 days. These data show that the use of RBCs as carriers of L-asparaginase greatly improves the pharmacodynam ic parameters of the drug.