PHARMACOKINETICS OF 2,5-DIAZIRIDINYL-3,6-BIS(2-HYDROXYETHYLAMINO)-1,4-BENZOQUINONE (BZQ, NSC-224070) DURING A PHASE-I CLINICAL-TRIAL

Plasma levels of 2,5-diaziridinyl-3,6-bis(2-hydroxyethylamino)-1,4-benzoquinone (BZQ, NSC 224070) were measured in nine patients after i.v. administration of the drug during a Phase I trial. Our own isocratic high performance liquid chromatographic (HPLC) method with a sensitivity of 3 ng/ml was used to quantify BZQ. Patients receiving 18-60 mg BZQ i.v. showed α and β plasma decays with half-lives of 6.2 ± 1.5 (mean ± S.D.) and 24 ± 4 min respectively. The apparent volume of the central compartment was 12.2 ± 4.6 l, and the total volume of distribution was 33.6 ± 11.3 l. The calculated plasma AUCs were linearly related to dose. A marked similarity in kinetic parameters was found for BZQ and diaziquone (AZQ, NSC 182986), another diaziridinylbenzoquinone that has recently completed phase II clinical trials. © 1990.