Clinical pharmacology of 2,5'-diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone (AZQ).

2,5'-Diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone (AZQ) is an alkylating compound which has exhibited a broad spectrum of antitumor activity against a variety of experimental tumors, particularly those implanted intracranially. We have studied the clinical pharmacology of AZQ in 11 patients with various types of tumors. AZQ was administered at 1-12 mg/m2 daily for 5 days by i.v. infusion in 10-30 min. 14C-labelled AZQ was given on day 1 only. Blood and urine specimens were analyzed radiochemically and chromatographically. The plasma disappearance of unchanged AZQ was essentially biphasic, with an initial plasma t 1/2 of 1.4 +/- 0.4 hr and a terminal t 1/2 of 45.5 +/- 3.1 hr. The apparent volume of distribution was 14.2 +/- 3.0 l/kg. The cumulative urinary excretion of unchanged AZQ was 4.3% in 24 hr and 8.6% in 96 hr. The total clearance of the drug was 200 ml/kg/hr. Cerebrospinal fluid AZQ concentration peaked 45-90 min after drug administration, reaching about 70% of that in plasma, and then declined at nearly the same rate.