RT Journal Article
SR Electronic
T1 Polyethylene glycol-L-asparaginase and L-asparaginase studies in rabbits.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 27
OP 29
VO 16
IS 1
A1 Ho, D H
A1 Wang, C Y
A1 Lin, J R
A1 Brown, N
A1 Newman, R A
A1 Krakoff, I H
YR 1988
UL http://dmd.aspetjournals.org/content/16/1/27.abstract
AB 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.