Erucylphosphocholine is the prototype of i.v. injectable alkylphosphocholines

Erucylphosphocholine (ErPC) is a new alkylphosphocholine derivative with di stinctly reduced hemolytic activity, thus allowing intravenous (i.v.) injec tion. ErPC was investigated in methylnitrosourea-induced rat mammary carcin oma, the signal tumor for these classes of alkylphosphocholines, using pero ral (p.o.) and i.v. dosages ranging from 15- 120 mu mol/kg/day. After 5 wee ks of treatment, i.v. administration of ErPC was not only equipotent to p.o . administration at three to five times lower doses but also caused complet e remissions in more than 50% of the animals. Such responses were not obtai ned with p.o. administration of ErPC or hexadecylphosphocholine (HPC, milte fosine); they demonstrate a distinctly improved therapeutic efficacy of i.v . ErPC in the model investigated. Moreover, since i.v. ErPC reduces the dru g load to the gastrointestinal tract, which is the main target of alkylphos phocholine-related side effects, such effects are expected to be diminished with this mode of treatment. In addition, ErPC was compared with HPC, the clinically used standard alkylphosphocholine, in a panel of 10 tumor cell l ines. On a molar basis, ErPC was less active than HPC in four of six tumor cell lines derived from solid tumors, but more active in three of four leuk emic cell lines. The overall similar sensitivity profiles of ErPC and HPC i ndicate that the advantage of ErPC seen in vivo, at least in part, is due t o improved pharmacokinetic properties. (C) 1988 Prous Science. All rights r eserved.