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Effects of the Src inhibitor saracatinib (AZD0530) on renal function in healthy subjects

R Neil Dalton1, Raj Chetty, Mary Stuart

  • 1WellChild Laboratory, King's College London, Evelina Children's Hospital, Lambeth Palace Road, London SE1 7EH, U.K. neil.dalton@kcl.ac.uk

Anticancer Research
|August 5, 2010
PubMed
Abstract

Insights

Saracatinib increases plasma creatinine by reducing tubular secretion, not by affecting kidney filtration. This effect was not clinically significant in healthy subjects.

Area of Science:

  • Pharmacology
  • Nephrology
  • Oncology

Background:

  • Saracatinib (AZD0530) is an investigational Src inhibitor for cancer therapy.
  • Previous studies noted increased plasma creatinine in healthy subjects receiving saracatinib.
  • This study aimed to elucidate the mechanism behind saracatinib-induced creatinine elevation.

Purpose of the Study:

  • To investigate the renal handling of creatinine following saracatinib administration.
  • To determine if saracatinib impacts glomerular filtration rate (GFR) or tubular secretion.

Main Methods:

  • A randomized, placebo-controlled study in 56 healthy males.
  • Single-dose (500 mg) and multiple-dose (125 mg for 14 days) saracatinib regimens were evaluated.
  • Inulin clearance and tubular creatinine secretion were assessed.

Main Results:

  • Saracatinib administration reduced the creatinine fractional excretion ratio.
  • This reduction was attributed to decreased tubular secretion of creatinine.
  • No significant changes in GFR or creatinine production were observed.

Conclusions:

  • The increase in plasma creatinine is due to reduced tubular secretion, not impaired kidney function.
  • The observed changes in plasma creatinine were not considered clinically relevant.

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