Clinical pharmacology of intramuscularly administered L-asparaginase.

Clinical pharmacology of L-asparaginase was compared by intramuscular and intravenous injections in 12 patients with metastatic cancer or leukemia. Following a single intramuscular injection at the gluteal site of L-asparaginase (10,000 IU/m2), the enzyme appeared in plasma as measured initially at 1 hour, but plateau levels were not reached in plasma until 14 to 24 hours after drug administration. The peak plasma level was 1.12 IU/ml, only one fourth of that seen when L-asparaginase was given intravenously at equal doses. However, the enzyme level decrease in the plasma after intramuscular injections was slower, with a half-life ot 46 hours, compared to 7 to 28 hours for intravenously administered drug. The apparent volume of distribution indicated that the intravenously injected enzyme was mostly distributed in plasma, whereas the intramuscularly injected enzyme yielded a much larger volume of distribution (63 versus 245 ml/kg). In addition, only 19 per cent of the intramuscularly injected dose was in plasma, and the area under the curve (C X t) was only 1/24 that by intravenous route (20 versus 487 IU/ml.hr). No enzyme was measurable in patients' urine samples collected for three days after intramuscular injections of the enzyme, and only a trace (less than 1 per cent) of the enzyme was detected in urine after intravenous administration.