Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Reed, G.A. et al.

Reed, Arneson, Putnam, Smith, Gray, Sullivan, Mayo, Crowell, Hurwitz,

Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane.

We have completed a phase I trial in women of the proposed chemopreventive natural product indole-3-carbinol (I3C). Women received oral doses of 400, 600, 800, 1,000, and 1,200 mg I3C. Serial plasma samples were analyzed by high-performance liquid chromatography-mass spectrometry for I3C and several of its condensation products. I3C itself was not detectable in plasma. The only detectable I3C-derived product was 3,3'-diindolylmethane (DIM). Mean C(max) for DIM increased from 61 ng/mL at the 400-mg I3C dose to 607 ng/mL following a 1,000-mg dose. No further increase was observed following a 1,200-mg dose. A similar result was obtained for the area under the curve, which increased from 329 h ng/mL at the 400-mg dose to 3,376 h ng/mL after a 1,000-mg dose of I3C. Significant interindividual quantitative variation was seen in plasma DIM values within each dosing group, but the overall profiles were qualitatively similar, with no quantifiable DIM before dosing, t(max) at approximately 2 h, and DIM levels near or below 15 ng/mL (the limit of quantitation), by 24 h. Different results were obtained for 14 subjects who received a 400-mg dose of I3C after 8 weeks of twice-daily I3C dosing. Although the predose sampling occurred at least 12 h after the last known ingestion of I3C, 6 of 14 subjects exhibited C(max) for DIM in their predose plasma. Despite this high initial value, plasma DIM for all subjects decreased to near or below the limit of quantitation within the 12-h sampling period. Possible reasons for this disparity between apparent t(1/2) of DIM and the high predose values are discussed. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2477-81).[1]

References

Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. Reed, G.A., Arneson, D.W., Putnam, W.C., Smith, H.J., Gray, J.C., Sullivan, D.K., Mayo, M.S., Crowell, J.A., Hurwitz, A. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]

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