Pharmacokinetic studies of daunorubicin in patients with acute myeloid leukemia

Although progress has been made in pharmacokinetic areas, incomplete knowledge of the relationship between cytotoxic drug concentration-time profiles and drug effects has remained an obstacle for optimization of therapy. We assumed that estimation of drug concentrations in plasma and tissue may help to explain why individuals have different responses to treatment with the drug. Since the targets of the cytostatic therapy in AML patients, i.e., the circulating leukemic cells and the leukemic cells in the bone marrow are easily accessible, these patients offer a unique opportunity to study the pharmacokinetics in different pharmacological compartments. Therefore, it was our objective to simultaneously monitor the DNR concentrations attained in vivo in blood and bone marrow of patients with AML during the RI treatment. In an attempt to estimate the predictive value of cellular DNR concentrations in AML, we tried to elucidate possible relationships between the cellular pharmacokinetic parameters of DNR and: a) the plasma distribution kinetics of the drug, b) the tumor load of the patient and, c) the clinical response to treatment. In addition, a preclinical study was planned in the rat with the purpose of investigating certain aspects of cellular DNR pharmacokinetics in pharmacological compartments that are not accessible in man.