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

Huali Wu,1 Ramesh K Ramanathan,2 Beth A Zamboni,3 Sandra Strychor,4 Suresh Ramalingam,5 Robert P Edwards,4 David M Friedland,4 Ronald G Stoller,4 Chandra P Belani,4 Lauren J Maruca,4 Yung-Jue Bang,6 William C Zamboni11UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, US...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Wu H, Ramanathan RK, Zamboni BA, Strychor S, Ramalingam S, Edwards RP, Friedl, DM, Stoller RG, Belani CP, Maruca LJ, Bang YJ, Zamboni WC
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://doaj.org/article/aabcd19fae254a208e2df1d1184be083
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:aabcd19fae254a208e2df1d1184be083
record_format dspace
spelling oai:doaj.org-article:aabcd19fae254a208e2df1d1184be0832021-12-02T02:06:53ZMechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients1176-91141178-2013https://doaj.org/article/aabcd19fae254a208e2df1d1184be0832012-10-01T00:00:00Zhttp://www.dovepress.com/mechanism-based-model-characterizing-bidirectional-interaction-between-a11319https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Huali Wu,1 Ramesh K Ramanathan,2 Beth A Zamboni,3 Sandra Strychor,4 Suresh Ramalingam,5 Robert P Edwards,4 David M Friedland,4 Ronald G Stoller,4 Chandra P Belani,4 Lauren J Maruca,4 Yung-Jue Bang,6 William C Zamboni11UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA; 2Translational Research Division, The Translational Genomics Research Institute, Scottsdale, AZ, USA; 3Department of Mathematics, Carlow University, Pittsburgh, PA, USA; 4School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 5Winship Cancer Institute, Emory University, Atlanta, GA, USA; 6College of Medicine, Seoul National University, Seoul, KoreaAbstract: 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®. 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.Keywords: population pharmacokinetics, pharmacodynamics, PEGylated liposome, nonlinear kineticsWu HRamanathan RKZamboni BAStrychor SRamalingam SEdwards RPFriedlDMStoller RGBelani CPMaruca LJBang YJZamboni WCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5555-5564 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wu H
Ramanathan RK
Zamboni BA
Strychor S
Ramalingam S
Edwards RP
Friedl
DM
Stoller RG
Belani CP
Maruca LJ
Bang YJ
Zamboni WC
Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients
description Huali Wu,1 Ramesh K Ramanathan,2 Beth A Zamboni,3 Sandra Strychor,4 Suresh Ramalingam,5 Robert P Edwards,4 David M Friedland,4 Ronald G Stoller,4 Chandra P Belani,4 Lauren J Maruca,4 Yung-Jue Bang,6 William C Zamboni11UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA; 2Translational Research Division, The Translational Genomics Research Institute, Scottsdale, AZ, USA; 3Department of Mathematics, Carlow University, Pittsburgh, PA, USA; 4School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 5Winship Cancer Institute, Emory University, Atlanta, GA, USA; 6College of Medicine, Seoul National University, Seoul, KoreaAbstract: 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®. 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.Keywords: population pharmacokinetics, pharmacodynamics, PEGylated liposome, nonlinear kinetics
format article
author Wu H
Ramanathan RK
Zamboni BA
Strychor S
Ramalingam S
Edwards RP
Friedl
DM
Stoller RG
Belani CP
Maruca LJ
Bang YJ
Zamboni WC
author_facet Wu H
Ramanathan RK
Zamboni BA
Strychor S
Ramalingam S
Edwards RP
Friedl
DM
Stoller RG
Belani CP
Maruca LJ
Bang YJ
Zamboni WC
author_sort Wu H
title Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients
title_short Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients
title_full Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients
title_fullStr Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients
title_full_unstemmed Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients
title_sort mechanism-based model characterizing bidirectional interaction between pegylated liposomal ckd-602 (s-ckd602) and monocytes in cancer patients
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/aabcd19fae254a208e2df1d1184be083
work_keys_str_mv AT wuh mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT ramanathanrk mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT zamboniba mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT strychors mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT ramalingams mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT edwardsrp mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT friedl mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT dm mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT stollerrg mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT belanicp mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT marucalj mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT bangyj mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
AT zamboniwc mechanismbasedmodelcharacterizingbidirectionalinteractionbetweenpegylatedliposomalckd602sckd602andmonocytesincancerpatients
_version_ 1718402725829410816