Comparative Pharmacokinetics of Chlorambucil and Melphalan in Man

Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells

“…The concentration of both cyclophosphamide or melphalan within the bone marrow of patients undergoing high dose chemotherapy will be variable even after doses are adjusted for body surface area or weight, as there is considerable pharmacokinetic variability among patients receiving chemotherapy [42]. The drug concentrations used to treat MSCs in this study were therefore based on the mean peak concentrations of either cyclophosphamide or melphalan observed in the plasma of patients undergoing high-dose chemotherapy treatments [27][28][29][30][31].…”

“…Cells prior to each experiment were incubated with each treatment for 48 hours in DMEM, 10% FCS. The concentrations used for each chemotherapeutic agent used were determined from published data of plasma concentrations from patients undergoing intensive high-dose chemotherapy treatment or pre-stem cell transplant conditioning [27][28][29][30][31].…”

Pharmacokinetics of Chlorambucil in Patients with Chronic Lymphocytic Leukaemia: Comparison of Different Days, Cycles and Doses

“…According to pharmacological textbooks, the elimination half-life varies between 1 and 2 hr (Vozeh et al 1990;Jack 1992;Benet et al 1996;Dollery 1999). The mean apparent elimination half-life of chlorambucil was 1.1 hr in patients with chronic lymphocytic leukaemia (Hartvig et al 1988), and 1.5 to 1.8 hr in patients with varying haematological disorders and normal renal function (Alberts et al 1980;Newell et al 1983). In these studies the elimination phase has been assumed to be monophasic, and data on the decreasing slope have been fitted into 1-exponential function.…”

“…Chlorambucil is rapidly and passively absorbed from the gastrointestinal tract after oral administration (Alberts et al 1980;Newell et al 1983;Adair & McElnay 1986;Hartvig et al 1988;Lind & Ardiet 1993). In the fasting state, oral bioavailability is between 70% and 90% (Newell et al 1983;Oppitz et al 1989;Jack 1992), but food decreases it significantly .…”

The clinical pharmacology of chlorambucil and prednimustine [letter]

“…chlorambucil. This is not necessarily deleterious since the only chlorambucil metabolite identified to date in man, phenyl acetic mustard (Newell et al, 1978;McLean et al, 1979;Alberts et al, 1980), is an active alkylating agent.…”