Organ distribution and tumor uptake of liposome entrapped cis-bis-neodecanoato trans-R, R-1,2 diaminocyclohexane platinum (II) administered intravenously and into the proper hepatic artery.
Blood and tissue levels of elemental platinum (Pt) were measured after the administration of a liposomally entrapped cisplatin analogue, cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP). In mice bearing subcutaneous B16 melanoma tumors, Pt tumor levels were not significantly different in animals treated i.v. with an equimolar dose of L-NDDP or cisplatin. In rabbits bearing liver tumors of VX2 carcinoma, i.v. administration of L-NDDP resulted in 2- to 20-fold higher Pt levels in all tissues (including VX2 tumors) except the brain and peripheral nerve than in animals treated with an equimolar dose of cisplatin. Compared with i.v. administration, inoculation of either drug into the proper hepatic artery resulted in a severalfold increase of Pt levels in the VX2 tumors. Blood and other tissue levels were not substantially changed by intraarterial (i.a.) administration. These studies show that (1) multilamellar lipid vesicles can adequately deliver a lipophilic cisplatin analogue (NDDP) to nonphagocytic tumors when administered i.v. and (2) the inoculation of L-NDDP into the proper hepatic artery results in higher Pt tumor levels than with i.v. administration but does not decrease the systemic distribution of the drug.
Khokhar
A R
AR
Department of Medical Oncology, University of Texas System Cancer Center, M.D. Anderson Hospital & Tumor Institute, Houston 77030.
Wright
K
K
Siddik
Z H
ZH
Perez-Soler
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010984:Platinum / Q000378:metabolism; D011817:Rabbits; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II); D010984:Platinum; D002945:Cisplatin