Polyethylene glycol-L-asparaginase and L-asparaginase studies in rabbits

• Published in: Drug metabolism and disposition Vol. 16; no. 1; p. 27
• Main Authors: Ho, D H, Wang, C Y, Lin, J R, Brown, N, Newman, R A, Krakoff, I H
• Format: Journal Article
• Language: English
• Published: United States 01.01.1988
• Subjects: Amino Acids - blood; Animals; Asparaginase - blood; Asparaginase - pharmacokinetics; Asparagine - blood; Aspartic Acid - blood; Half-Life; In Vitro Techniques; Male; Polyethylene Glycols - blood; Polyethylene Glycols - pharmacokinetics; Rabbits
• ISSN: 0090-9556; 1521-009X

Injections of polyethylene glycol (PEG)-L-asparaginase or L-asparaginase were given to two rabbits each at doses of 40 units/kg. Ten min following injection of either enzyme preparation, the plasma enzyme concentration was approximately 1 unit/ml. This level decreased steadily in the rabbits given L-asparaginase, with a t1/2 of approximately 20 hr. In contrast, the enzyme level in rabbits given PEG-L-asparaginase decreased much more slowly, with a t1/2 of approximately 144 hr. The slower disappearance rate of PEG-L-asparaginase resulted in greater values for the area under the concentration versus time curve and smaller values for total clearance. Immediately following the enzyme injections, no L-asparagine could be detected in the plasma, and a transient elevation of L-aspartic acid levels was noted. By 4 hr, the L-aspartic acid level in all of the rabbits returned to near normal. The L-asparagine, however, was not measurable as long as plasma enzyme was detectable. Levels of L-asparagine returned to normal 4 days after L-asparaginase administration, and 27 days elapsed before L-asparagine was detected in rabbits given PEG-L-asparaginase.