PHARMACOKINETIC BEHAVIOR AND ANTINEOPLASTIC ACTIVITY OF LIPOSOMAL HEXADECYLPHOSPHOCHOLINE

Hexadecylphosphocholine (HePC) shows remarkable antineoplastic efficac y in Sprague-Dawley rats bearing methylnitrosourea-induced mammary car cinoma. Unfortunately, this is accompanied by detrimental side effects that include gastrointestinal damage, body weight loss, and thromboph lebitis after i.v. injection, which has precluded the use of the HePC in humans, where nausea and vomiting can occur at noneffective dose le vels. We have developed small unilamellar vesicles (SUVs) composed of HePC, cholesterol, and 1,2-dipalmitoyl-sn-gly cero-3-phosphoglycerol, which can be given p. o. and i.v. In contrast to the free drug, the to xicity of liposomal HePC is shown to be greatly reduced, and there is no risk of thrombophlebitis. Single administration of equimolar HePC d oses results in differing pharmacokinetic values for free HePC (p. o.) and HePC-SUVs (p. o., i.v.).