| Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors. | |
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MedLine Citation:
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PMID: 20626314 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Background: 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. Methods: 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. Results: 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). Conclusions: Monocytes are more sensitive to S-CKD602, compared with neutrophils, and the increased sensitivity is related to the liposomal formulation, not CKD-602. These results suggest that monocytes engulf S-CKD602, which causes the release of CKD-602 from the liposome and toxicity to the monocytes, and that the effects are more prominent in patients <60. |
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Authors:
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William C Zamboni; Lauren J Maruca; Sandra Strychor; Beth A Zamboni; Suresh Ramalingam; Robert P Edwards; Jk Kim; Yj Bang; Hy Lee; David M Friedland; Ronald G Stoller; Chandra P Belani; Ramesh K Ramanathan |
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Publication Detail:
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Type: Journal Article Date: 2010-07-14 |
Journal Detail:
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Title: Journal of liposome research Volume: 21 ISSN: 1532-2394 ISO Abbreviation: J Liposome Res Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9001952 Medline TA: J Liposome Res Country: England |
Other Details:
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Languages: eng Pagination: 158-65 Citation Subset: IM |
Affiliation:
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Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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