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Pharmacokinetics of SN2310, an injectable emulsion that incorporates a new derivative of SN-38 in patients with advanced solid tumors.

Authors
  • Marier, Jean-Francois
  • Pheng, Leng
  • Trinh, My My
  • Burris, Howard A 3rd
  • Jones, Suzanne
  • Anderson, Kirsten
  • Warner, Serina
  • Porubek, David
Type
Published Article
Journal
Journal of Pharmaceutical Sciences
Publisher
Elsevier
Publication Date
September 2011
Volume
100
Issue
10
Pages
4536–4545
Identifiers
DOI: 10.1002/jps.22645
PMID: 21630281
Source
Medline
Keywords
License
Unknown

Abstract

SN2310 is an injectable emulsion composed of vitamin E, a succinate derivative, as well as 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan. Single intravenous doses of 15, 20, 25, and 30 mg/m(2) of SN2310 emulsion were administered in a total of 26 patients with advanced solid malignancies. Serial blood samples were collected and concentrations of SN2310, SN-38, and SN-38 glucuronide were assayed. Mean systemic clearance of SN2310 ranged between 1.91 and 2.02 L/h/m(2) . Peak concentrations of SN-38 were observed at the end of infusion, suggesting a fast metabolic conversion of SN2310 to its active form, SN-38. Mean t1/2 values of SN-38 across the 20-30 mg/m(2) dose levels (131-199 h) were 33-55-fold longer than those observed for SN2310. The systemic exposure of SN-38 increased in a proportional manner over the dose range studied. SN2310 emulsion displayed an improved safety profile as compared with irinotecan. The most significant safety risk was neutropenia. Considering the rapid formation of SN-38, the proportional increase in exposure levels, and its longer elimination half-life, less frequent dosing of SN2310 emulsion may be considered for the treatment of patients with advanced solid malignancies.

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