Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors.
J Liposome Res
; 21(2): 158-65, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-20626314
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Sistema Fagocitário Mononuclear
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Camptotecina
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Inibidores da Topoisomerase I
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Lipossomos
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Neoplasias
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
J Liposome Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos