High-Dose Busulfan – Monitoring of Plasma Levels and Dosage Modificationsin Adults

Overview

Bone marrow and peripheral blood stem cell transplantations, despite their curative potential, still carry significantrisks for patients. Toxicity of high-dose chemotherapy is one of the leading causes of peritransplant mortality.Busulfan is a frequently used chemotherapeutic agent in conditioning regimens prior to transplantations. The choiceof the optimal busulfan dose and prediction of its clinical effect may be very difficult. Absorption of busulfan fromgastrointestinal tract and its metabolism can vary considerably. Several studies published recently showed that thebusulfan plasma concentrations correlate better with the clinical effect and extramedullary toxicity caused by thisdrug than with the actual dose administered to the patient. Approximate target plasma concentrations of busulfan,which meet the optimal balance between the clinical effect and the risk of severe side effects of chemotherapy, wereproposed. Almost twenty chromatographic methods were published, which make the quantitative measurement ofbusulfan possible. The maintanance of certain busulfan plasma concentration during its whole administration withthe help of the repeated adjustments of its dosage can reduce the toxicity caused by this agent and improve the resultsof bone marrow or peripheral blood stem cell transplantations. This method is easily applicable, has low financaland personal demands, and technical appliances, which it requires are usually accessible in most transplant centerlaboratories.

Key words:
busulfan, pharmacokinetics, dose modifications, area under the curve, chromatography, bone marrowtransplantation.