Related Experiment Videos
Diosmin pretreatment affects bioavailability of metronidazole
K Rajnarayana1, Mada S Reddy, Devarakonda R Krishna
1Drug Metabolism and Clinical Pharmacokinetics Division, University College of Pharmaceutical Sciences, Kakatiya University, AP-506009, Warangal, India.
European Journal of Clinical Pharmacology
|April 17, 2003
Summary
Diosmin pretreatment significantly alters metronidazole metabolism in healthy volunteers, increasing drug plasma levels and reducing metabolite excretion. This suggests diosmin may inhibit cytochrome P450 enzymes, impacting drug interactions.
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Investigation
Background:
- Cytochrome P450 enzymes play a crucial role in drug metabolism.
- Understanding potential drug-drug interactions is vital for patient safety.
- Diosmin is a flavonoid with potential medicinal properties.
Purpose of the Study:
- To investigate the inhibitory effects of diosmin on cytochrome P450-mediated metronidazole metabolism.
- To assess changes in metronidazole pharmacokinetics and metabolism following diosmin pretreatment.
Main Methods:
- A before/after non-blinded study was conducted in 12 healthy male volunteers.
- Volunteers received metronidazole alone or after 9 days of diosmin pretreatment.
- Serum and urinary concentrations of metronidazole and its metabolites were measured using high-performance liquid chromatography.
Main Results:
- Diosmin pretreatment significantly increased metronidazole plasma AUC(0-inf) by 27% and Cmax by 24%.
- Time to peak concentration (tmax) of metronidazole was not significantly affected.
- Urinary excretion of metronidazole metabolites decreased, while unchanged metronidazole excretion increased.
Conclusions:
- Diosmin pretreatment significantly alters metronidazole metabolism in healthy volunteers.
- Observed changes in pharmacokinetics and urinary metabolite recovery suggest diosmin may inhibit cytochrome P450 enzymes.
- This interaction highlights the potential for diosmin to influence the metabolism of other drugs processed by CYP450 enzymes.