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Population Pharmacokinetics of Pegylated Liposomal CKD-602 (S-CKD602) in Patients With Advanced Malignancies

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Wu, Huali; Ramanathan, Ramesh K.; Zamboni, Beth A.; Strychor, Sandra; Ramalingam, Suresh; Edwards, Robert P.; Friedland, David M.; Stoller, Ronald G.; Belani, Chandra P.; Maruca, Lauren J.; Bang, Yung-Jue; Zamboni, William C.

Issue Date
SAGE Publications
Journal of Clinical Pharmacology, Vol.52 No.2, pp.180-194
S-CKD602 is a pegylated long-circulating liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. A population pharmacokinetic (PK) model for encapsulated and released CKD-602 following administration of S-CKD602 was developed to assess factors that may influence S-CKD602 PK. Plasma samples from 45 patients with solid tumors were collected in a phase 1 study. S-CKD602 was administered as a 1-hour intravenous infusion with doses ranging from 0.1 to 2.5 mg/m(2). Plasma concentrations of encapsulated and released CKD-602 were used to develop a population PK model using NONMEM. PK of encapsulated CKD-602 was described by a 1-compartment model with nonlinear clearance, and PK of released CKD-602 was described by a 2-compartment model with linear clearance for all patients. Covariate analysis revealed that tumor in the liver was a significant covariate for clearance of encapsulated CKD-602 and that age significantly influenced the release rate of CKD-602 from S-CKD602. Maximum elimination rate in patients with liver tumor is 1.5-fold higher compared with patients without liver tumor. Release rate of CKD-602 from S-CKD602 in patients less than 60 years old was 2.7-fold higher compared with patients 60 years old or older. These observations have potential implications in the optimal dosing of liposomal agents.
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  • Department of Medicine
Research Area Clinical Medicine


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