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bcp4364-sup-0001-FigureS1.doc34K

Figure S1

Concentration–time profile of mean (± SD, n = 8) piperine plasma concentration after enzymatic deconjugation. Measurements were performed using samples collected at 1.25 h prior to administration of a single oral dose of flurbiprofen, paracetamol or midazolam and then every 2 h post dose up to 10 h. Three doses of curcuminoid/piperine treatment were administered approximately 23, 14 and 1 h prior to flurbiprofen, paracetamol or midazolam dosage and then at 4 h post dose

bcp4364-sup-0002-FigureS2.doc66K

Figure S2

Concentration–time profiles of mean (± SD, n = 8) curcumin (A), demethoxycurcumin (B) and bisdemethoxycurcumin (C) plasma concentrations after enzymatic deconjugation. Measurements were performed using samples collected at 1.25 h prior to administration of a single oral dose of flurbiprofen, paracetamol or midazolam and then every 2 h post dose up to 10 h. Three doses of curcuminoid/piperine treatment were administered approximately 23, 14 and 1 h prior to flurbiprofen, paracetamol or midazolam dosage and then at 4 h post dose

bcp4364-sup-0003-FigureS3.doc57K

Figure S3

Pharmacodynamic effect–time profiles of mean (± SD, n = 8) self-rated sedation (A), observer-rated sedation (B) and DSST score (C) changes from pre dose baseline following a single 3 mg oral dose of midazolam preceded by placebo or curcuminoid/piperine treatment. No significant differences were found between curcuminoid/piperine treatment and placebo (P > 0.05; t-test on ranks)

bcp4364-sup-0004-FigureS4.doc49K

Figure S4

Pharmacodynamic effect–time profiles of mean (± SD, n = 8) % relative EEG beta amplitude reported as raw values (A) or with pre dose (baseline) value subtraction (B) following a single 3 mg oral dose of midazolam preceded by placebo or curcuminoid/piperine treatment. No significant differences were found between curcuminoid/piperine treatment and placebo (P > 0.05; t-test on ranks)

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