3,3’-Diindolylmethane Exhibits Significant Metabolism After Oral Dosing in Humans

Vermillion-Maier, Monica; Siddens, Lisbeth E.; Uesugi, Sandra; Choi, Jaewoo; Leonard, Scott; Pennington, Jamie; Tilton, Susan C.; Smith, Jordan N.; Ho, Emily; Chow, Sherry; Nguyen, Bach D.; Kolluri, Siva K.; Williams, David E.

doi:10.1124/dmd.120.000346

3,3’-Diindolylmethane Exhibits Significant Metabolism After Oral Dosing in Humans

Journal Article · Sun Aug 01 00:00:00 EDT 2021 · Drug Metabolism and Disposition

DOI:https://doi.org/10.1124/dmd.120.000346· OSTI ID:1827145

Vermillion-Maier, Monica ^[1]; Siddens, Lisbeth E. ^[1]; Uesugi, Sandra ^[1]; Choi, Jaewoo ^[1]; Leonard, Scott ^[1]; Pennington, Jamie ^[1]; Tilton, Susan C. ^[1]; Smith, Jordan N. ^[2]; Ho, Emily ^[1]; Chow, Sherry ^[3]; Nguyen, Bach D. ^[1]; Kolluri, Siva K. ^[1]; Williams, David E. ^[1]

Oregon State University
BATTELLE (PACIFIC NW LAB)
University of Arizona

3,3’-Diindolylmethane (DIM), a major phytochemical derived from ingestion of cruciferous vegetables such as Brussels sprouts, is also a dietary supplement. In preclinical models, DIM is an effective cancer chemopreventive agent and has been studied in a number of clinical trials. Previous pharmacokinetic studies in preclinical and clinical models have not reported DIM metabolites in plasma or urine following oral dosing and the pharmacological actions of DIM on target tissues is assumed to be solely via the parent compound. Seven subjects (6 males and 1 female) ranging from 26-65 years of age, on a cruciferous vegetable-restricted diet prior to and during the study, took 2 BioResponse-DIM® 150 mg capsules (45.3 mg DIM/capsule) in the evening for one week with a final dose the morning of the first blood draw. A complete time course was performed with plasma and urine collected over 48 hours and analyzed by UPLC-MS/MS. In addition to parent DIM, two mono-hydroxylated (2-ox- and 3-methylenehydroxy-DIM) and 1 dihydroxylated (3-methylenehydroxy-2-ox-DIM) metabolites, along with their sulfate and glucuronide conjugates, were present in both plasma and urine. The results reported here are indicative of significant phase 1 and phase 2 metabolism and differ from previous pharmacokinetic studies in rodents and humans which reported only parent DIM present following oral administration.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1827145

Report Number(s):: PNNL-SA-158910

Journal Information:: Drug Metabolism and Disposition, Journal Name: Drug Metabolism and Disposition Journal Issue: 8 Vol. 49

Country of Publication:: United States

Language:: English

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