Pharmacokinetics of liposome encapsulated cisplatin in rats.

The chemotherapeutic anticancer agent Cisplatin--cis-diamine-dichloroplatinum (II)--has several disadvantages, such as its extreme nephrotoxicity, fast elimination via the kidneys, and rapid binding to plasma proteins. Encapsulation into negatively charged, multilamellar liposomes (MLV), composed of egg-lecithin: cholesterol: dicetylphosphate in 5:5:1 molar ratio, causes drastic changes in behavior after a single i.v. injection: marked increase in the circulation half life paralleled by slower urinary excretion; remarkedly higher levels of free drug in the blood; increased uptake in liver, spleen and lymph nodes, and decreased uptake in skin and bones. In the kidneys a reduced and retarded uptake over 15 hr, then a higher uptake was found. The liposomal Cisplatin has a strong transitory diuretic effect, which nevertheless is not paralleled by other signs of renal injury such as decreased output of creatinine or increased output of protein or urinary enzymes. By pre-ejection of empty liposomes the diuresis can be reduced and the additional Pt deposit in the kidneys prevented.