Hibiscus Tea Increased Four-Hour Metoprolol Plasma Concentration Without Altering CYP1A2 or CYP2D6 Activity in Healthy Volunteers

چکیده

Background: Hibiscus sabdariffa tea inhibits eight major human cytochrome P450 (CYP) enzymes in vitro; its in vivo effects remain unclear.

Objectives: To evaluate whether standardised hibiscus tea inhibits CYP1A2 and CYP2D6 or modifies their probe substrate (caffeine and metoprolol) plasma concentrations.

Materials and methods: In an open-label, randomized, two-period crossover study, 24 healthy non-smoking volunteers received caffeine 200 mg and metoprolol 50 mg with 300 mL water or standardized hibiscus tea. Plasma caffeine, paraxanthine, metoprolol, and α-hydroxymetoprolol were measured four hours post-dose. CYP1A2 and CYP2D6 inhibition were assessed indirectly through decreased paraxanthine/caffeine and increased metoprolol/α-hydroxymetoprolol metabolic ratios (MRs), respectively.

Results: Metoprolol MR increased from 4.97 ± 3.22 to 5.13 ± 3.20 (p=0.8058); caffeine MR remained 0.15 ± 0.02 in both conditions. Hibiscus tea was associated with a 56% higher four-hour metoprolol plasma concentration.

Conclusions: A single dose of standardised hibiscus tea did not alter either caffeine or metoprolol MR at four hours post-dose but was associated with higher metoprolol concentration. These findings do not exclude CYP-mediated effects or establish a change in total drug exposure. Full pharmacokinetic studies are needed to clarify the mechanism and clinical relevance.