Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors

Journal of Liposome Research
William C ZamboniRamesh K Ramanathan

Abstract

STEALTH(®) liposomal CKD-602 (S-CKD602), a camptothecin analog, is eliminated by the reticuloendothelial system (RES), which consists of cells, including monocytes. We evaluated the relationship between monocyte and absolute neutrophil counts (ANCs) in the blood and pharmacokinetic disposition of S-CKD602 and nonliposomal CKD-602 (NL-CKD602) in patients. As part of a phase I study of S-CKD602 and phase I and II studies of NL-CKD602, the percent decreases in ANC and monocytes at their nadir were calculated. After S-CKD602, the amount of CKD-602 recovered in urine was measured. For S-CKD602 in patients <60 years, the percent decrease in ANC and monocytes were 43  ±  31 and 58  ±  26%, respectively (P = 0.001). For S-CKD602 in patients ≥60, the percent decrease in ANC and monocytes were 41  ±  31 and 45  ±  36%, respectively (P =  0.50). For NL-CKD602 (n = 42), the percent decrease in ANC and monocytes were similar (P >  0.05). For S-CKD602, the relationship between the percent decrease in monocytes and CKD-602 recovered in urine was stronger in patients <60 (R(2) =  0.82), compared with patients ≥60 (R(2) =  0.30). Monocytes are more sensitive to S-CKD602, compared with neutrophils, and the increased sensitivity is related to the...Continue Reading

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Citations

Aug 31, 2013·European Journal of Clinical Pharmacology·Huali WuWilliam C Zamboni
May 19, 2011·Cancer Chemotherapy and Pharmacology·Ninh M La-BeckWilliam C Zamboni
Jun 7, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·William C ZamboniPiotr Grodzinski
Nov 26, 2013·Advanced Drug Delivery Reviews·Nicolas BertrandOmid C Farokhzad
Feb 16, 2012·Journal of Liposome Research·Gina SongWilliam C Zamboni
Jul 16, 2015·Expert Opinion on Drug Metabolism & Toxicology·Andrew T LucasWilliam C Zamboni
Feb 6, 2016·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Andrew T LucasWilliam C Zamboni
Feb 25, 2015·Nanomedicine·Jennifer S PetschauerWilliam C Zamboni
Oct 18, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Andrew T LucasWilliam C Zamboni
Dec 20, 2016·Nature Nanotechnology·Fangfang ChenDmitri Simberg
Apr 5, 2012·Clinical Pharmacology and Therapeutics·W P CaronW C Zamboni
Sep 18, 2013·The Journal of Pharmacology and Experimental Therapeutics·Whitney P CaronWilliam C Zamboni
Aug 25, 2011·Journal of Pharmacokinetics and Pharmacodynamics·Whitney P CaronWilliam C Zamboni
Apr 27, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Whitney P CaronWilliam C Zamboni
Sep 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gina SongWilliam C Zamboni
Dec 23, 2020·Nature Nanotechnology·Wen JiangBetty Y S Kim
Mar 23, 2021·Acta Pharmaceutica Sinica. B·Iara Maíra de Oliveira VianaNicolas Bertrand
Jul 3, 2021·Journal of Personalized Medicine·Md Abdus SubhanVladimir P Torchilin

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