ArticleCurrent drug metabolism2012
Catabolic fate and pharmacokinetic characterization of trastuzumab emtansine (T-DM1): an emphasis on preclinical and clinical catabolism.
Article in Current drug metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 135 citations in OpenAlex.
- Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody-drug conjugate in development for the treatment of HER2-positive cancer.Cancer chemotherapy and pharmacology · 2012Trial
- Payload-Based Clinical Pharmacology Review of Approved Antibody-Drug Conjugates: Commonalities and Considerations for Streamlined Development.Clinical pharmacology and therapeutics · 2026Review
- Trastuzumab Emtansine-Associated Porto-Sinusoidal Vascular Disorder: Clinical Features and Outcomes from Published Cases.Journal of clinical medicine · 2026Review
- A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Impact of trastuzumab emtansine (T-DM1) on spleen volume in patients with HER2-positive metastatic breast cancer.Japanese journal of clinical oncology · 2025Article
- Article
- Systemic oncological therapy in breast cancer patients on dialysis.World journal of clinical oncology · 2024Review
- Current Analytical Strategies for Antibody-Drug Conjugates in Biomatrices.Molecules (Basel, Switzerland) · 2022Review
- Stepping forward in antibody-drug conjugate development.Pharmacology & therapeutics · 2022Review
- Advances in Antibody-Drug Conjugates in the Treatment of HER2-Positive Breast Cancer.Breast cancer (Dove Medical Press) · 2022Review
- Trastuzumab does not bind rat or mouse ErbB2/neu: implications for selection of non-clinical safety models for trastuzumab-based therapeutics.Breast cancer research and treatment · 2022Article
- The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively.Cancer medicine · 2021Review
- Preclinical Characterization of the Distribution, Catabolism, and Elimination of a Polatuzumab Vedotin-Piiq (POLIVYJournal of clinical medicine · 2021Article
- Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer.Cell death & disease · 2021Article
- Analytical Methods for the Detection and Quantification of ADCs in Biological Matrices.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Current LC-MS-based strategies for characterization and quantification of antibody-drug conjugates.Journal of pharmaceutical analysis · 2020Review
- Mertansine Inhibits mRNA Expression and Enzyme Activities of Cytochrome P450s and Uridine 5'-Diphospho-Glucuronosyltransferases in Human Hepatocytes and Liver Microsomes.Pharmaceutics · 2020Article
- ADME Considerations and Bioanalytical Strategies for Pharmacokinetic Assessments of Antibody-Drug Conjugates.Antibodies (Basel, Switzerland) · 2018Review
- Article
- Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted epigenetic modulation.Chemical science · 2018Article
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12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate in clinical development for the treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers. Herein, we describe a series of studies to assess T-DM1 absorption, distribution, metabolism, and excretion (ADME) in rats as well as to assess human exposure to T-DM1 catabolites. Following administration of unlabeled and radiolabeled T-DM1 in female Sprague Dawley rats as a single dose, plasma, urine, bile and feces were assessed for mass balance, profiling and identification of catabolites. In rats, the major circulating species in plasma was T-DM1, while DM1 concentrations were low (1.08 to 15.6 ng/mL). The major catabolites found circulating in rat plasma were DM1, [N-maleimidomethyl] cyclohexane-1- carboxylate-DM1 (MCC-DM1), and Lysine-MCC-DM1. These catabolites identified in rats were also detected in plasma samples from patients with HER2-positive metastatic breast cancer who received single-agent T-DM1 (3.6 mg/kg every 3 weeks) in a phase 2 clinical study. There was no evidence of tissue accumulation in rats or catabolite accumulation in human plasma following multiple dosing. In rats, T-DM1 was distributed nonspecifically to the organs without accumulation. The major pathway of DM1-containing catabolite elimination in rats was the fecal/biliary route, with up to 80% of radioactivity recovered in the feces and 50% in the bile. The rat T-DM1 ADME profile is likely similar to the human profile, although there may be differences since trastuzumab does not bind the rat HER2- like receptor. Further research is necessary to more fully understand the T-DM1 ADME profile in humans.
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