Effect of food on the Oral Bioavailability of Berberine and Monacolin Administered in Combination in Healthy Male Volunteers

Objectives: To investigate the effect of food on the bioavailability of a combination of monacolin and berberine in healthy volunteers. Methods: Eighteen male volunteers received a single recommended oral dose of the combination under fasted conditions (reference) and fed conditions (high fat meal; test), in a randomized, open label, crossover fashion. Plasma concentrations of berberine, monacolin and its metabolite were measured by LC-MS/MS. Pharmacokinetic parameters were determined by non-compartmental analysis. No effect of food was assumed if the 90% CIs (confidence intervals) for estimated ratio test/reference was included in the acceptance limits 0.80-1.25 for phenotyping metrics AUCt and Cmax. Key findings: For berberine, the Cmax and AUCt test/reference ratios were 2.97 and 2.69, respectively, and relevant 90% CIs (2.25-3.91 and 2.15-3.36, respectively) were above the acceptance limit. For lovastatin hydroxy acid, the active metabolite of monacolin, the test/reference ratios were 1.18 (Cmax) and 0.98 (AUCt). The 90% CIs fell entirely within the acceptance limit for AUCt, (0.85-1.13), whereas the upper bound of the 90% CIs for Cmax (1.01-1.37) was just above the predefined interval. Conclusions: Food intake significantly increases berberine bioavailability and does not significantly affect monacolin bioavailability when these two extracts are administered in combination.