Human pharmacology and toxicology of succinylated Acinetobacter glutaminase-asparaginase.

AGA3 also had a very short half-life in humans (8). Chemical modification of free amino groups can increase the plasma half-life of some asparaginase and glutaminase-aspa raginase enzymes in animals (12, 20). In previous studies, we have shown that treatment of AGA with succinic anhydnide produces a uniform preparation with the same catalytic activity and physical properties, but with an increased plasma half-life in mice, rats, and rabbits. Succinylated enzyme preparations have now been tested in 20 children with leukemia and other tumors refractory to conventional chemotherapy. This report describes the human pharmacology of the succinylated AGA and its effect on amino acid levels in plasma, cerebrospinal fluid, and urine. A preliminary report has appeared describing the antitumor activity and toxicity in the first 14 patients (9).