This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Reed, G. A. Articles by Hurwitz, A. PubMed PubMed Citation Articles by Reed, G. A. Articles by Hurwitz, A. Related Collections Clinical Intervention Clinical Intervention: Early-Phase (I/II) Clinical or Translational Trials

Single-Dose Pharmacokinetics and Tolerability of Absorption-Enhanced 3,3'-Diindolylmethane in Healthy Subjects

Departments of ¹ Pharmacology, Toxicology, and Therapeutics; ² Internal Medicine; ³ Dietetics and Nutrition; and ⁴ Biostatistics, and the ⁵ Kansas Masonic Cancer Research Institute, University of Kansas Medical Center, Kansas City, Kansas; and ⁶ Chemopreventive Agent Development Research Group, National Cancer Institute, Bethesda, Maryland

Requests for reprints: Gregory A. Reed, MS 1018, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160. Phone: 913-588-7513; Fax: 913-588-7501. E-mail: greed{at}kumc.edu

We have completed a single ascending dose clinical study of the proposed chemopreventive agent 3,3'-diindolylmethane (DIM). The study agent was nutritional-grade, absorption-enhanced BioResponse 3,3'-diindolylmethane (BR-DIM). We determined the safety, tolerability, and pharmacokinetics of single doses of BR-DIM in drug-free, non-smoking, healthy men and women. Groups of four subjects were enrolled for each dose level. After randomization, one subject in each group received placebo whereas three received active BR-DIM. The doses administered were 50, 100, 150, 200, and 300 mg, with the 300-mg dose repeated in an additional group. No BR-DIM–related adverse effects were reported at doses up to 200 mg. At the 300-mg dose, one of six subjects reported mild nausea and headache and one also reported vomiting. Only the latter effect was judged as probably related to the study agent. Analysis of serial plasma samples showed that only one subject at the 50-mg dose had detectable concentrations of DIM. The single 100-mg dose of BR-DIM resulted in a mean maximum plasma concentration (C_max) of 32 ng/mL and a mean area under the curve (AUC) of 128 h ng/mL, and a single 200-mg dose produced a mean C_max of 104 ng/mL and a mean AUC of 553 h ng/mL. The single 300-mg dose of BR-DIM resulted in a mean C_max of 108 ng/mL and a mean AUC of 532 h ng/mL. We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the dose to 300 mg did not result in an increase in C_max. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2619–24)