Summary
Healthy mice were treared intravenously with the antileukemic L-asparaginase A by a single injection of 5,000 U/kg. At various times after injection the L-asparaginase (Asnase) content was determined in the blood-plasma and in the whole body; furthermore the simultaneous content of L-asparagine (Asn) was determined in the whole animal.
Methods are described for the determination of Asnase and Asn in whole mice.
The Asnase activity in the blood-plasma decreased rapidly during the first 4 hours after application. Afterwards an equilibrium of distribution was apparently reached, and the further decrease followed first order kinetics with a half-life of 3 h approximately.
In the whole animal, the Asnase decrease followed from the beginning first order kinetics with a half-time of 3 h. After reaching the equilibrium, the relative volume of distribution was approximately 0.1 l/kg.
In untreated mice the mean total Asn content was 26 nmoles per g. After Asnase application Asn fell, in just over one hour, below the detection limit. After two days it began to reincrease slowly; only after several days the initial value was found.
The experiments have shown that Asnase also exhibits its effect apart from the circulation. It is concluded that the disturbance of the blood-mediated Asn supply is not the essential effect on sensitive cells. The problem of Asnase distribution and its influence on sensitive and resistant cells is discussed with regard to the reported results.
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A part of this publication was presented by I. Flenker as thesis at the Med. Fakultaet of the University of Bonn (1) and was reported by J. Puetter (2) on the Symposium international sur la L-asparaginase.
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Puetter, J., Flenker, I. The behavior of L-asparaginase and L-asparagine in whole mice after asparaginase-application. European Journal of Drug Metabolism and Pharmacokinetics 1, 149–154 (1976). https://doi.org/10.1007/BF03189269
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DOI: https://doi.org/10.1007/BF03189269