Pharmacokinetics of Promensil

The plasma and urinary profiles of isoflavones resulting from acute and chronic administration of Promensil were measured during a study involving 16 healthy men and women ⁴³. The participants were given one Promensil tablet in the morning after an overnight fast. Venous plasma and urine were collected at intervals for 24 h. After this time, two tablets were administered each day for 2 weeks, and samples collected over a 48 h period after the last dose.

The study demonstrated that:

• Biochanin A, formononetin, genistein and daidzein all appeared rapidly in plasma, achieving maximum concentrations by 4-6 h post dose. Contrary to previous understanding, these data demonstrate that biochanin A and formononetin are not completely demethylated to form genistein and daidzein and therefore have additional biological effects to their demethylated counterparts.


• The plasma half-lives of each of the isoflavones following chronic administration were 12-16 h, long enough to allow once-daily dosing.
  
  
• administration of one 40 mg tablet daily produced plasma levels similar to those found in populations consuming high-isoflavone diets ⁴⁴.

Biochanin A, formononetin, genistein and daidzein undergo extensive structural modification in the body ^45-47. There are two main sites of isoflavone metabolism, the gut and liver. The liver is responsible for demethylation of 60% of biochanin A and formononetin to form genistein and daidzein, respectively (Figure 4) ^48-50. Approximately 30-70% of the dietary isoflavones are converted into active metabolites by the gut flora. The active metabolites detected in urine following Promensil administration are equol, o-desmethylangolensin, dihydrodaidzein and dihydrogenistein (Figure 5).

_Figure 4. Metabolism of isoflavones

_Figure 5. HPLC analysis of urine 24 hours after a single tablet of Promensil

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