Diosmin pretreatment affects bioavailability of metronidazole

To screen for inhibitory effects of diosmin on cytochrome P(450)-mediated metabolism of metronidazole in healthy volunteers. Before/after non-blinded investigation conducted in healthy male volunteers. After an overnight fast, metronidazole (two 400-mg tablets) was administered to 12 volunteers, eit...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2003-04, Vol.58 (12), p.803-807
Main Authors: RAJNARAYANA, K, REDDY, Mada S, KRISHNA, Devarakonda R
Format: Article
Language:English
Subjects:
Adult
Anti-Infective Agents - administration & dosage
Anti-Infective Agents - blood
Anti-Infective Agents - pharmacokinetics
Anti-Infective Agents - urine
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiparasitic agents
Area Under Curve
Biological and medical sciences
Biological Availability
Cardiovascular system
Cytochrome P-450 Enzyme Inhibitors
Diosmin - pharmacology
Drug Interactions
Half-Life
Humans
Male
Medical sciences
Metronidazole - blood
Metronidazole - pharmacokinetics
Metronidazole - urine
Pharmacology. Drug treatments
Vascular wall
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Summary:To screen for inhibitory effects of diosmin on cytochrome P(450)-mediated metabolism of metronidazole in healthy volunteers. Before/after non-blinded investigation conducted in healthy male volunteers. After an overnight fast, metronidazole (two 400-mg tablets) was administered to 12 volunteers, either alone or after a 9-day pretreatment period with a once-daily dose of diosmin 500-mg tablets under direct observation. Serum concentrations of metronidazole up to 48 h postdose and urinary concentrations of metronidazole and its two major metabolites up to 24 h postdose were measured using reversed-phase high-performance liquid chromatography. Metronicazole plasma AUC((0- infinity )) and C(max) were significantly higher after diosmin pretreatment by (mean) 27% and 24%, respectively. However, time to reach peak concentration (t(max)) was not affected significantly. Urinary excretion of acid and hydroxy metabolites in urine was decreased significantly, while excretion of unchanged metronidazole was increased. Diosmin pretreatment significantly altered the metabolism of metronidazole, as demonstrated by changes in plasma pharmacokinetics as well as by urinary recovery of both parent drug and its major metabolites. This may be caused by the inhibition of cytochrome P(450) enzymes.
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-002-0543-5