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A single ascending dose, initial clinical pharmacokinetic and safety study of ursolic acid in healthy adult volunteers (1044.6)
Author(s) -
Hirsh Steven,
Huber Luke,
Zhang Peter,
Stein Richard,
Joyal Steven
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1044.6
Subject(s) - ursolic acid , bioavailability , pharmacokinetics , absorption (acoustics) , chemistry , pharmacology , medicine , chromatography , physics , acoustics
Objective: To assess the safety and pK parameters after administration of a single ascending oral dose of ursolic acid. Methods : 14 subjects were administered a single oral ascending dose of ursolic acid 100mg, 500mg and 1000mg. pK assessements were conducted at pre‐dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, 24 hr and 48 hr. Safety assessments were also conducted. Results : Statistical analysis was conducted for 11 subjects who had completed the trial with no serious adverse events reported. For the 100mg dose: 4 subjects‐ ursolic content was noted at 5 timepoints at 0.5hr‐8hr with 4 timepoints‐ levels were lower than LLOQ (lower limit of quantification‐10.5ng/ml) and in 7 subjects, ursolic acid content was not observed. For the 500mg dose: ursolic acid content was observed in 6 subjects at 12 timepoints at 1‐12hr with 10 timepoints‐the levels were lower than LLOQ and in 5 subjects, ursolic acid content was not observed. For the 1000mg dose: ursolic acid content was observed in 9 subjects at 21 timepoints at 1‐12 hr with 12 timepoints‐the levels were lower than LLOQ and in 2 subjects, ursolic acid content was not observed. Conclusion : These results revealed low and variable bioavailability for oral ursolic acid in human subjects. Possible reasons could include: Poor water solubility with decreased absorption and rapid elimination, metabolism by the gut wall and liver with poor intestinal absorption. Metabolism of ursolic acid by the human gut microbiome may yield variability in the peak plasma levels. Human peak level results differ remarkably from the peak levels observed in the preclinical animal research.