The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

Abstract

It has been shown that lymphocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia do not modify the mustard group of chlorambucil, as has been demonstrated previously in Yoshida ascites cells. However, lymphocytes from patients with an unsatisfactory clinical course or poor response to treatment were able to modify the aromatic region of the drug molecule; little change occurred in the aromatic absorption of intracellular chlorambucil in patients who responded to treatment. This simple test may provide a rapid assessment of a patient's potential response to chemotherapy.

Population pharmacokinetics identifies rapid gastrointestinal absorption and plasma clearance of oral chlorambucil administered to cats with indolent lymphoproliferative malignancies

“…The mechanism of chlorambucil absorption is thought to occur by passive diffusion in the proximal small intestinal tract, 20 which would support the rapid peak plasma concentrations seen here and explain why cobalamin concentrations were not identified as a covariate. However, passive diffusion also occurs with chlorambucil into malignant lymphocytes, 21,22 and-depending on tumor burden within the GI tract-this may influence the concentration of drug absorbed from the GI tract into the plasma. The PK of chlorambucil in healthy cats has not been performed, and therefore the variability observed in our study cannot be compared to a more homogeneous population; this may have also affected our ability to evaluate more fully the contributions of covariates to the observed variability.…”