relation: http://d-scholarship-dev.library.pitt.edu/18051/
title: Plasma and tissue disposition of non-liposomal DB-67 and liposomal DB-67 in C.B-17 SCID mice
creator: Zamboni, WC
creator: Jung, LL
creator: Strychor, S
creator: Joseph, E
creator: Zamboni, BA
creator: Fetterman, SA
creator: Sidone, BJ
creator: Burke, TG
creator: Curran, DP
creator: Eiseman, JL
description: Purpose: DB-67 is a silatecan, 7-silyl-modified camptothecin, with enhanced lipophilicity and increased blood stability of the active-lactone ring. The generation of a liposomal formulation of DB-67 may be an attractive method of intravenous (IV) administration and may maintain DB-67 in the active-lactone form. We evaluated the tissue and plasma disposition of DB-67 lactone and hydroxy acid after administration of non-liposomal (NL) and liposomal (L) DB-67 in severe combined immunodeficient (SCID) mice. Methods: NL-DB-67 and L-DB-67 10 mg/kg IV×1 were administered via a tail vein in SCID mice. After dosing, mice (n=3 per time point) were euthanized and blood (∼1 ml) and tissue were collected from 5 min to 48 h after administration. DB-67 lactone and hydroxy acid concentrations in plasma and DB-67 total (sum of lactone and hydroxyl acid) concentrations in tissues were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. Results: Clearance of DB-67 lactone after administration of NL-DB-67 and L-DB-67 were 1.6 and 3.5 l/h/m 2, respectively; DB-67 lactone half-lives after administration of NL-DB-67 and L-DB-67 were 1.4 and 0.9 h, respectively. The percentages of DB-67 lactone in plasma after administration of NL-DB-67 and L-DB-67 were 92% and 89%, respectively. Liver, kidney, spleen, and lung tissues had longer exposure times to DB-67 after administration of L-DB-67 compared with NL-DB-67. Conclusion: In plasma, the majority of DB-67 remained in the lactone form after administration of NL-DB-67 and L-DB-67. The plasma disposition of DB-67 was similar after administration of NL-DB-67 and L-DB-67, suggesting that most of the DB-67 is immediately released from the L-DB-67 formulation. Following administration of L-DB-67, the higher and longer exposure of DB-67 in the spleen, as compared with NL-DB-67, is consistent with splenic clearance of liposomes by the reticuloendothelial system. © 2007 Springer Science+Business Media, LLC.
date: 2008-10-01
type: Article
type: PeerReviewed
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/18051/1/licence.txt
identifier:   Zamboni, WC and Jung, LL and Strychor, S and Joseph, E and Zamboni, BA and Fetterman, SA and Sidone, BJ and Burke, TG and Curran, DP and Eiseman, JL  (2008) Plasma and tissue disposition of non-liposomal DB-67 and liposomal DB-67 in C.B-17 SCID mice.  Investigational New Drugs, 26 (5).  399 - 406.  ISSN 0167-6997     
relation: 10.1007/s10637-007-9109-9