Metronidazole Topical and Milk Thistle: Interaction Details

a) The concomitant administration of silymarin (a flavonoid extract of milk thistle) and metronidazole significantly accelerated the total body clearance of metronidazole and significantly reduced metronidazole exposure. In a pharmacokinetic, 2-phase study, healthy volunteers (n=12) first received a 3-day oral regimen of metronidazole 400 milligrams (mg) 3 times daily, followed by a single dose of metronidazole 400 mg on day four, after which blood and urine samples were analyzed over the next 48 hours. After a 4-day washout period, each subject received a 9-day regimen of oral silymarin 140 mg daily, with metronidazole 400 mg given 3 times daily concurrently for days 7 through 9. On day 10, metronidazole 400 mg was given, after which blood and urine samples were again analyzed over 48 hours. Compared with metronidazole alone, concomitant administration of silymarin with metronidazole significantly accelerated the mean total body clearance of metronidazole (by 42%, p less than 0.05) and its active metabolite hydroxyl-metronidazole (by 47%, p less than 0.001). Metronidazole mean area under the concentration-time curve (AUC; 0-48 hours) and mean maximum plasma concentration (Cmax) were both significantly reduced with concurrent silymarin treatment (from 230.58 to 166.22 mg x hour/milliliter (mg x hr/mL) and from 16.91 to 12.00 mg/mL respectively; p less than 0.0001, both measures); similar reductions occurred in AUC (0-48 hours; from 125.86 to 89.37 mg x hr/mL) and Cmax (from 4.56 to 3.65 mg/mL) (p less than 0.0001 and 0.01, respectively) for the active metabolite hydroxyl-metronidazole. The half-life of hydroxyl-metronidazole also declined significantly in the presence of silymarin (by 33%, p less than 0.01). The study authors suggest that silymarin induction of intestinal p-glycoprotein serves as the probable mechanism of action ¹.