home > drugs a-z list > metronidazole injection (metronidazole injection) drug center > metronidazole injection (metronidazole injection) drug - clinical pharmacology

Metronidazole is a synthetic antibacterial compound. Disposition of metronidazole (metronidazole (metronidazole injection) injection) in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of eight hours.

The major route of elimination of metronidazole (metronidazole (metronidazole injection) injection) and its metabolites is via the urine (60–80% of the dose), with fecal excretion accounting for 6–15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(β-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid] and glucuronide conjugation, with unchanged metronidazole (metronidazole (metronidazole injection) injection) accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10 mL/min/1.73 m².

Metronidazole (metronidazole (metronidazole injection) injection) is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole (metronidazole (metronidazole injection) injection) is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria.

Metronidazole (metronidazole (metronidazole injection) injection) appears in cerebrospinal fluid, saliva, and human milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole (metronidazole (metronidazole injection) injection) have also been detected in pus from hepatic abscesses.

Plasma concentrations of metronidazole (metronidazole (metronidazole injection) injection) are proportional to the administered dose. An eight-hour intravenous infusion of 100–4,000 mg of metronidazole (metronidazole (metronidazole injection) injection) in normal subjects showed a linear relationship between dose and peak plasma concentration.

In patients treated with a 0.5% intravenous solution of metronidazole (metronidazole (metronidazole injection) injection) using a dosage regimen of 15 mg/kg loading dose followed six hours later by 7.5 mg/kg every six hours, peak steady-state plasma concentrations of metronidazole (metronidazole (metronidazole injection) injection) averaged 25 mcg/mL with trough (minimum) concentrations averaging 18 mcg/mL.

Decreased renal function does not alter the single-dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole (metronidazole (metronidazole injection) injection) is decreased in patients with decreased liver function.

In one study newborn infants appeared to demonstrate diminished capacity to eliminate metronidazole (metronidazole (metronidazole injection) injection) . The elimination half-life, measured during the first three days of life, was inversely related to gestational age. In infants whose gestational ages were between 28 and 40 weeks, the corresponding elimination half-lives ranged from 109 to 22.5 hours.

Microbiology

Metronidazole (metronidazole (metronidazole injection) injection) is active in vitro against most obligate anaerobes, but does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes. Against susceptible organisms, metronidazole (metronidazole (metronidazole injection) injection) is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations. Metronidazole (metronidazole (metronidazole injection) injection) has been shown to have in vitro and clinical activity against the following organisms:

Anaerobic gram-negative bacilli, including:

Bacteroides species, including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus) Fusobacterium species

Anaerobic gram-positive bacilli, including:

Clostridium species and susceptible strains of Eubacterium

Anaerobic gram-positive cocci, including:

Peptococcus niger Peptostreptococcus species

Susceptibility Tests

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to metronidazole (metronidazole (metronidazole injection) injection) ; however, the rapid, routine susceptibility testing of individual isolates of anaerobic bacteria is not always practical, and therapy may be started while awaiting these results.

Quantitative methods give the most accurate estimates of susceptibility to antibacterial drugs. A standardized agar dilution method and a broth microdilution method are recommended.¹

Control strains are recommended for standardized susceptibility testing. Each time the test is performed, one or more of the following strains should be included: Clostridium perfringens ATCC 13124, Bacteroides fragilis ATCC 25285, and Bacteroides thetaiotaomicron ATCC 29741. The mode metronidazole (metronidazole (metronidazole injection) injection) MICs for those three strains are reported to be 0.25, 0.25 and 0.5 mcg/mL, respectively.

A clinical laboratory test is considered under acceptable control if the results of the control strains are within one doubling dilution of the mode MICs reported for metronidazole (metronidazole (metronidazole injection) injection) .

A bacterial isolate may be considered susceptible if the MIC value for metronidazole (metronidazole (metronidazole injection) injection) is not more than 16 mcg/mL. An organism is considered “resistant” if the MIC is greater than 16 mcg/mL. A report of "resistant" from the laboratory indicates that the infecting organism is not likely to respond to therapy.

REFERENCES

¹ Proposed standard: PSM-11 — Proposed Reference Dilution Procedure for Antimicrobic Susceptibility Testing of Anaerobic Bacteria, National Committee for Clinical Laboratory Standards, and Sutter, et al.: Collaborative Evaluation of a Proposed Reference Dilution Method of Susceptibility Testing of Anaerobic Bacteria, Antimicrob. Agents Chemother. 16:495–502 (Oct.) 1979; and Tally, et al.: In Vitro Activity of Thienamycin, Antimicrob.

Last reviewed on RxList: 6/19/2009
This monograph has been modified to include the generic and brand name in many instances.