Antibacterial activity and pharmacokinetics of nitroimidazoles. A review

Abstract

The antibacterial activity of metronidazole and tinidazole are comparable. The former is subject to biotransformation with the production of both hydroxy-metronidazole and acetylmetronidazole. The hydroxylated moiety has an antibacterial activity and may act either synergistically or additively in combination with metronidazole, thus enhancing the therapeutic activity of the latter. Metronidazole and tinidazole may be given both orally and parenterally. The bioavailability of oral doses of metronidazole is 88-95%, that of tinidazole 90%. Rectal suppositories have a bioavailability of 60-70%. The serum half-life of metronidazole is 6-10 hours, that of hydroxy-metronidazole 9.5-19 hours, and that of tinidazole 9-14 hours. The half-life may be longer in patients who have undergone colorectal surgery. Renal failure enhances the elimination of hydroxy-metronidazole and acetyl-metronidazole, whereas the consequences for unchanged metronidazole are negligible. The effect of reduced renal function on tinidazole is unclear. The extravascular penetration of metronidazole and tinidazole are similar. A single prophylactic intravenous dose of 1500 mg of either drug causes prolonged antibacterial effects which would last 36-48 hours for both drugs.