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Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease
Author(s) -
Eradiri Okponanabofa,
Jamali Fakhreddin,
Thomson Alan B. R.
Publication year - 1988
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bod.2510090210
Subject(s) - metronidazole , sulfasalazine , pharmacokinetics , pharmacology , volume of distribution , metabolite , cimetidine , drug interaction , chemistry , urine , phenobarbital , prednisone , antibacterial agent , excretion , medicine , antibiotics , ulcerative colitis , biochemistry , disease
The influence of prednisone( PR ), sulfasalazine( SZ ), cimetidine( CM ), and pheno‐barbital(PB) on the pharmacokinetics of metronidazole was investigated in six Chrohn's patients. Metronidazole was first administered alone ( 250 mg bid, po ) and then with prednisone ( 10mg bid, po), sulfasalazine (lg bid, po), cimetidine ( 600mg bid ) or phenobarbital ( 60 mg bid, po). Each regimen was followed for 6 days and sampling of blood and urine was carried out on the 7th day after the first dose of each regimen. Plasma and urine samples were analysed for the drug and its two principal metabolites, hydroxymetronidazole and metronidazole‐1‐acetic acid, by HPLC. When given alone, metronidazole had a mean volume of distribution of 0.667 ± 0.15 1kg −1 , a half‐life of 9.7 ± 3.1 h and an oral clearance of 0.852 ± 0.23 ( ml −1 min ) kg −1 . The disposition kinetics of metronidazole and its metabolites was not altered by CM and SZ. Induction of metabolism of metronidazole by PR was made manifest in significant increases in oral clearance of the former and urinary excretion of the hydroxy metabolite, and significant decrease in AUC of the parent compound. PB also induced the metabolism of metronidazole. This induction was reflected in significant increases in the oral clearance of metronidazole and AUC of the hydroxy metabolite as well as significant decreases in AUC, half‐life, and urinary excretion of the parent drug.