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 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 i.u. 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.i.u.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.
Kravtzoff
R
R
Laboratoire de Biopharmacologie Transfusionnelle, INSERM U316, CRTS, Tours, France.
Desbois
I
I
Lamagnere
J P
JP
Muh
J P
JP
Valat
C
C
Chassaigne
M
M
Colombat
P
P
Ropars
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D006207:Half-Life; D006801:Humans; D007553:Isotope Labeling; D008875:Middle Aged; D009994:Osmolar Concentration; D009996:Osmotic Fragility
D000970:Antineoplastic Agents; D004337:Drug Carriers; D001215:Asparaginase