THE CORRELATION OF RESPONSE WITH PLASMA PHARMACOKINETICS AND POLYAMINE CONCENTRATIONS IN PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA RECEIVINGAMONAFIDE

We have investigated the correlation of clinical responses (decreases of white blood cells and peripheral blasts) with pharmacokinetic and p harmacodynamic parameters in patients with acute myelogenous leukemia who are receiving amonafide. The increase of plasma polyamine concentr ations was used as a measure of tumor sensitivity (pharmacodynamic eff ect). The correlations between pharmacokinetic parameters (biological half life, area under the concentration time curve (AUC), total plasma clearance), decreases of total white blood cells and peripheral leuke mic blasts were weak (maximum r = 0.47). Correlations of response with polyamines were better than those with pharmacokinetic parameters, bu t not exceptional; of these, the best correlations were with the incre ase of putrescine. On the other hand, correlations of combinations of AUC and increases of plasma polyamine concentrations with decreases of total white blood cell counts approached unity. Unexpectedly, decreas es of peripheral leukemic blasts were correlated just as well with put rescine increase alone (r = 0.91, P = 0.003) or with a combination of polyamine, increases and AUC (r = 0.92, P = 0.036).