Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents.

Unlabelled: A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Inter-patient PK variability of 9 liposomal and SM formulations of the same drug was evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range).

Synthesis and characterization of DNA minor groove binding alkylating agents.

Derivatives of methyl 3-(1-methyl-5-(1-methyl-5-(propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl)-1H-pyrrol-3-ylamino)-3-oxopropane-1-sulfonate (1), a peptide-based DNA minor groove binding methylating agent, were synthesized and characterized. In all cases, the N-terminus was appended with an O-methyl sulfonate ester, while the C-terminus group was varied with nonpolar and polar side chains. In addition, the number of pyrrole rings was varied from 2 (dipeptide) to 3 (tripeptide).

Plasma and tissue disposition of non-liposomal DB-67 and liposomal DB-67 in C.B-17 SCID mice.

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.