Pharmacokinetic behavior and antineoplastic activity of liposomal hexadecylphosphocholine

Hexadecylphosphocholine (HePC) shows remarkable antineoplastic efficacy in Sprague-Dawley rats bearing methylnitrosourea-induced mammary carcinoma. Unfortunately, this is accompanied by detrimental side effects that include gastrointestinal damage, body weight loss, and thrombophlebitis after i.v. injection, which has precluded the use of the HePC in humans, where nausea and vomiting can occur at noneffective dose levels. 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 toxicity of liposomal HePC is shown to be greatly reduced, and there is no risk of thrombophlebitis. Single administration of equimolar HePC doses results in differing pharmacokinetic values for free HePC (p.o.) and HePC-SUVs (p.o., i.v.).