PARENTERAL BUSULFAN FOR TREATMENT OF MALIGNANT DISEASE

摘要

Stable parenteral formulations of busulfan safe for parenteral administra- tion. An HPLC assay for busulfan sensitive enough to dependably quantitate concentrations in plasma as low as approximately 100 ng/ml was developed. Th e stability of these formulations was investigated to select preparations prov iding desirable plasma pharmacokinetic parameters with parenteral versus oral admi nis-tration. In addition, quantitative extraction techno logy was established for reliable quantification of bulsulfan in plasma samples after both oral and parenteral drug administration. When administered to experimental animals, the parenteral bu sul-fan formulation yielded significantly higher plasma drug concentrations and higher area under the plasma concentration vs. time curve than did the oral (standa rd) tablet preparation. The improved bioavailability of the parenteral formulati on op_ timizes high dose busulfan thepary against malignant disease and improves th e safety of such therapy.