Emily Chan
Faculty Member
Last active: 3/28/2014

Population pharmacokinetics of PEGylated liposomal CPT-11 (IHL-305) in patients with advanced solid tumors.

Wu H, Infante JR, Keedy VL, Jones SF, Chan E, Bendell JC, Lee W, Zamboni BA, Ikeda S, Kodaira H, Rothenberg ML, Burris HA, Zamboni WC
Eur J Clin Pharmacol. 2013 69 (12): 2073-81

PMID: 23989300 · DOI:10.1007/s00228-013-1580-y

PURPOSE - To investigate pharmacokinetics (PK) of encapsulated CPT-11, released CPT-11 and the active metabolite SN-38 following administration of IHL-305 and to identify factors that may influence IHL-305 PK.

METHODS - Plasma samples from 39 patients with solid tumors were collected in a phase I study. IHL-305 was administered as a 1 h IV infusion with doses ranging from 3.5 to 210 mg/m(2). Plasma concentrations of encapsulated CPT-11, released CPT-11 and SN-38 were used to develop a population PK model using NONMEM®.

RESULTS - PK of encapsulated CPT-11 was described by 1-compartment model with nonlinear clearance and PK of released CPT-11 was described by a 1-compartment model with linear clearance for all patients. PK of the active metabolite SN-38 was described by a 2-compartment model with linear clearance for all patients. Covariate analysis revealed that gender was a significant covariate for volume of distribution of encapsulated CPT-11. Vencap in male patients is 1.5-fold higher compared with female patients.

CONCLUSIONS - The developed population PK modeling approach is useful to predict PK exposures of encapsulated and released drug and can be applied to the more than 300 other nanoparticle formulations of anticancer agents that are currently in development. The effect of gender on PK of IHL-305 needs to be further evaluated.

MeSH Terms (14)

Adult Aged Antineoplastic Agents, Phytogenic Camptothecin Female Humans Infusions, Intravenous Irinotecan Liposomes Male Middle Aged Models, Biological Neoplasms Polyethylene Glycols

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