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Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients

Cited 7 time in Web of Science Cited 8 time in Scopus
Issue Date
2012-07
Citation
International journal of nanomedicine, Vol.7, pp.5555-5564
Keywords
population pharmacokineticspharmacodynamicsPEGylated liposomenonlinear kinetics
Abstract
S-CKD602 is a PEGylated liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. The objective of this study was to characterize the bidirectional pharmacokinetic-pharmacodynamic (PK-PD) interaction between S-CKD602 and monocytes. Plasma concentrations of encapsulated CKD-602 and monocytes counts from 45 patients with solid tumors were collected following intravenous administration of S-CKD602 in the phase I study. The PK-PD models were developed and fit simultaneously to the PK-PD data, using NONMEM (R). The monocytopenia after administration of S-CKD602 was described by direct toxicity to monocytes in a mechanism-based model, and by direct toxicity to progenitor cells in bone marrow in a myelosuppression-based model. The nonlinear PK disposition of S-CKD602 was described by linear degradation and irreversible binding to monocytes in the mechanism-based model, and Michaelis-Menten kinetics in the myelosuppression-based model. The mechanism-based PK-PD model characterized the nonlinear PK disposition, and the bidirectional PK-PD interaction between S-CKD602 and monocytes.
ISSN
1176-9114
URI
https://hdl.handle.net/10371/173115
DOI
https://doi.org/10.2147/IJN.S35751
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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