PARENTERAL BUSULFAN FOR TREATMENT OF MALIGNANT DISEASE

摘要

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