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Amrizole Actions |
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Pharmacology: Amrizole is a synthetic antibacterial compound. Disposition of Amrizole 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 Amrizole 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 Amrizole accounting for approximately 20% of the total. Renal clearance of Amrizole is approximately 10 mL/min/1.73 m2.
Amrizole 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 Amrizole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria.
Amrizole appears in cerebrospinal fluid, saliva and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of Amrizole have also been detected in pus from hepatic abscesses.
Plasma concentration of Amrizole are proportional to the administered dose. An eight hour intravenous infusion of 100-4,000 mg of Amrizole in normal subjects showed a linear relationship between dose and peak plasma concentration.
In patients treated with intravenous Amrizole, using a dosing 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 Amrizole averaged 25 mcg/mL with trough (minimum) concentrations averaging 18 mcg/mL.
Decreased renal function does not alter the single-dose pharmacokinetics of Amrizole. However, plasma clearance of Amrizole is decreased in patients with decreased liver function.
In one study newborn infants appeared to demonstrate diminished capacity to eliminate Amrizole. 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 10.9 to 22.5 hours.
Microbiology: Amrizole 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, Amrizole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations. Amrizole 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 species, Peptostreptococcus species.
Do not use Amrizole in or near the eyes. Watering of the eyes may occur when the medicine is used too close to the eyes.
If Amrizole does get into your eyes, wash them out immediately, but carefully, with large amounts of cool tap water. If your eyes still burn or are painful, check with your doctor.
Before applying Amrizole, thoroughly wash the affected area(s) with a mild, nonirritating cleanser, rinse well, and gently pat dry.
To use:
To help keep your rosacea under control, keep using Amrizole for the full time of treatment. You may have to continue using Amrizole every day for 9 weeks or longer. Do not miss any doses.
The dose of Amrizole will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Amrizole. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of Amrizole, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Take the extended-release Amrizole tablet (Amrizole) on an empty stomach, at least 1 hour before or 2 hours after eating a meal.
Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time.
Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Amrizole will not treat a viral infection such as the common cold or flu.
To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your liver function may also need to be tested. Visit your doctor regularly.
This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using Amrizole.
Store at room temperature away from moisture and heat.
Normal Subjects:
Following a single, intravaginal 5 gram dose of Amrizole Vaginal Gel (equivalent to 37.5 mg of Amrizole) to 12 normal subjects, a mean maximum serum Amrizole concentration of 237 ng/mL was reported (range: 152 to 368 ng/mL). This is approximately 2% of the mean maximum serum Amrizole concentration reported in the same subjects administered a single, oral 500 mg dose of Amrizole (mean Cmax = 12,785 ng/mL, range: 10,013 to 17,400 ng/mL). These peak concentrations were obtained in 6 to 12 hours after dosing with Amrizole Vaginal Gel and 1 to 3 hours after dosing with oral Amrizole.
The extent of exposure [area under the curve (AUC)] of Amrizole, when administered as a single intravaginal 5 gram dose of Amrizole Vaginal Gel (equivalent to 37.5 mg of Amrizole), was approximately 4% of the AUC of a single oral 500 mg dose of Amrizole (4977 ng-hr/mL and approximately 125,000 ng-hr/mL, respectively).
Dose-adjusted comparisons of AUCs demonstrated that, on a mg to mg comparison basis, the absorption of Amrizole, when administered vaginally, was approximately half that of an equivalent oral dosage.
Patients with Bacterial Vaginosis:
Following single and multiple 5 gram doses of Amrizole Vaginal Gel to 4 patients with bacterial vaginosis, a mean maximum serum Amrizole concentration of 214 ng/mL on day 1 and 294 ng/mL (range: 228 to 349 ng/mL) on day five were reported. Steady state Amrizole serum concentrations following oral dosages of 400 to 500 mg BID have been reported to range from 6,000 to 20,000 ng/mL.
Microbiology:
The intracellular targets of action of Amrizole on anaerobes are largely unknown. The 5-nitro group of Amrizole is reduced by metabolically active anaerobes, and studies have demonstrated that the reduced form of the drug interacts with bacterial DNA. However, it is not clear whether interaction with DNA alone is an important component in the bactericidal action of Amrizole on anaerobic organisms.
Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis.
Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens, Gardnerella vaginalis, Mobiluncus spp., and Mycoplasma hominis, has not been defined. Nonetheless, Amrizole is an antimicrobial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:
Bacteroides spp.
Gardnerella vaginalis
Mobiluncus spp.
Peptostreptococcus spp.
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Information checked by Dr. Sachin Kumar, MD Pharmacology
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