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. 2008 Jun;25(6):1309-17.
doi: 10.1007/s11095-007-9485-z.

Toxicological protein biomarker analysis--an investigative one-week single dose intravenous infusion toxicity and toxicokinetic study in cynomolgus monkeys using an antibody-cytotoxic conjugate against ovarian cancer

Frank Y Hsieh  1 , Elizabeth Tengstrand, Lily Y Li, Yuling N Huang, Mark N Milton, Lee Silverman, Carl Alden, Gerald Miwa, Frank Lee
Affiliations

Toxicological protein biomarker analysis--an investigative one-week single dose intravenous infusion toxicity and toxicokinetic study in cynomolgus monkeys using an antibody-cytotoxic conjugate against ovarian cancer

Frank Y Hsieh et al. Pharm Res. 2008 Jun.

Abstract

Introduction: Antibody-cytotoxic conjugates are complex novel therapeutic agents whose toxicological properties are not presently well understood. The objective of this study was to identify toxicological markers in serum that correlate with MLN8866 (an antibody-cytotoxic conjugate) exposure and related pathological events in monkeys.

Materials and methods: Cynomolgus monkeys were treated once with 5, 15, or 30 mg/kg MLN8866 via a 20 min intravenous infusion. MLN8866 exposure (Cmax and AUCO-4 day) was determined by quantifying MLN8866 levels in serum.

Results: The increase in MLN8866 exposure was approximately dose proportional. Two acute phase proteins in serum (serum amyloid A and haptoglobin) were correlated with MLN8866 exposure and toxicological outcomes (e.g., erythropoiesis and leucopoiesis).

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