Metronidazole dosages

A woman with vaginal trichomoniasis was given metronidazole on several occasions over the course of a year, but the infection flared up again as soon as it was stopped. When it was realised that she was also taking phenobarbital 100 mg daily, the metronidazole dosage was doubled to 500 mg three times daily, and she was cured after a 7-day course. A pharmacokinetic study found that the clearance of metronidazole was increased (half-life 3.5 hours compared with the normal half-life of 8 to 9 hours). ... 

A retrospective study in children who had not responded to metronidazole for giardiasis or amoebiasis found that 80% of them had been taking long-term phenobarbital. In a prospective study in 36 children the normal recommended metronidazole dosage had to be increased approximately threefold to 60 mg/kg to achieve a cure. The half-life of metronidazole in 15 other children taking phenobarbital was found to be 3.5 hours compared with the normal half-life of 8 to 9 hours. ... 

An established and clinically important interaction. Monitor the effects of concurrent use and anticipate the need to increase the metronidazole dosage two to threefold if phenobarbital is given. All of the barbiturates are potent liver enzyme inducers and would therefore be expected to interact similarly. 

The ciclosporin blood levels of a kidney transplant patient rose from 850 to 1930 nanograms/mL when metronidazole 2.25 g daily and cimetidine 800 mg daily were started. The levels fell to about 1500 nanograms/mL when the metronidazole dosage was halved and the eimetidine stopped. Beeause the levels of eielosporin were still so high, the dose of ciclosporin... 

Metronidazole was used as single therapy or associated with cotrimoxazole compared to placebo in patients with a symptomatic relapse of CD. At the end of the 4 weeks of treatment there was no difference in response among the three groups [36], In a Canadian study, two different dosages of metronidazole (10 and 20 mg/kg/daily) were used versus placebo in patients with active CD no difference was found between the two groups, but in the metronidazole-treated group there was a high rate of dropout because of side effects or intolerance [37],... 

Oral Following IV therapy, use oral metronidazole when conditions warrant. The usual adult oral dosage is 7.5 mg/kg every 6 hours (about 500 mg for a 70 kg adult). Do not exceed a maximum of 4 g in 24 hours. 

Elderly Because the pharmacokinetics of metronidazole may be altered in the elderly, monitoring of serum levels may be necessary to adjust the dosage accordingly. 

Talwar et al. reported a simultaneous spectrophotometric determination of diloxanide furoate and metronidazole in dosage forms [15]. The drug substances were extracted from tablets with methanol, and the extract diluted with 0.01 M sodium hydroxide. The absorbance of the solution was measured at 247 and 320 nm against 0.01 M sodium hydroxide, and the concentration of each individual drug was calculated by the Vierordt method. Drug recoveries were in the range of 99 to 100%, and the method was satisfactorily applied to the analysis of commercial samples. 

Das and Haider described a simultaneous spectrophotometrie method for the analysis of binary dosage form mixtures of diloxanide furoate with metronidazole or with tinidazole [19], Powdered tablets or suspension, equivalent to 50 mg of the drug substances, were dissolved in 50 mL of dimethylformamide with shaking. After 15 minutes, the solution was diluted to 100 mL with water and filtered. A 1 mL portion of the filtrate was diluted to 50 mL with water, and the absorbance of the resulting solution measured at 320 and 262 nm for metronidazole and diloxanide furoate simultaneously. Alternatively, readings were taken at 318 and 262 nm for the simultaneous determination of tinidazole and diloxanide furoate. Recoveries were reported to be quantitative. 

Sadana and Gaonkar have simultaneously determined diloxanide furoate and tinidazole in pharmaceutical dosage form by gas liquid chromatography [37]. Powdered tablets or suspension formulations were dissolved in chloroform, the solution filtered, and then diluted to 25 mL with chloroform. The solution also contained metronidazole as an internal standard. A 600 nL aliquot was analyzed on a stainless steel column (1 m X 3.2 mm) containing 3% of OV-17 on Chlorosorb W-UP (100-120 mesh). The GC system was operated at 200°C, using nitrogen as the carrier gas (45 mL/min). Flame ionization detection was used to observe the analytes. 

The separation and estimation of diloxanide furoate and metronidazole in solid dosage forms was reported by Bhoir et al., using packed column supercritical fluid chromatography [38], A JASCO Cig colunm (10 pm particle size, 25 cm x 4 mm) was used at 40°C, with an injection volume of 20 pL. The mobile phase consisted of 26% methanol in CO2 (flow rate of 2 mL/min), and operated at a pressure of 17.6 MPa. When detected on the basis of its ultraviolet absorbance at 230 nm, the retention time for the drug was 1.6 minutes. The linear region of the calibration graph was reported to be 20-70 pg/mL. 

El-gizawy reported the analysis of diloxanide furoate in its dosage forms by a HPLC method [40]. Furazol tablets containing 200 mg of metronidazole and 250 mg of diloxanide furoate were treated with 50 mL of methanol, sonicated for 10 minutes, and diluted to 100 mL with methanol. A portion of the resulting solution was centrifuged, and a 20 pL portion of the clear supernatant solution diluted to 10 mL with the mobile phase. This process yielded a final analyte concentration equivalent to 5 pg/mL. 20 pL aliquots of the solution were annualized by HPLC using a stainless steel column (10 cm x 4.6 mm) packed with Cyclobond I. The mobile phase consisted of 13 7 0.05 M phosphate buffer (pH 7) methanol (flow rate of 1 mL/min), and detection was performed at 254 nm. 

Rao et al. reported a high performance liquid chromatographic method to determine diloxanide furoate and metronidazole in single and in combined dosage forms [41]. A 30 mg equivalent of diloxanide furoate and 25 mg of metronidazole (either as the bulk drug substances or in powdered tablets) was dissolved in methanol, amidopyrine added as the internal standard, and the mixture analyzed by HPLC at room temperature. The analytical column (30 cm x 3.9 mm) consisted of p-Bondapak Cig, with 9 9 1 1 methanol water 0.05 M KH2PO4 0.05 M NaH2P04 as the mobile phase. The flow rate was 1 mL/min), and detection was performed at 254 nm. 

Metronidazole is indicated for treatment of anaerobic or mixed intra-abdominal infections, vaginitis (trichomonas infection, bacterial vaginosis), C difficile colitis, and brain abscess. The typical dosage is 500 mg three times daily orally or intravenously (30 mg/kg/d). Vaginitis may respond to a single 2-g dose. A vaginal gel is available for topical use. 

Metronidazole is the treatment of choice for giardiasis. The dosage for giardiasis is much lower—and the drug thus better tolerated—than that for amebiasis. Efficacy after a single treatment is about 90%. Tinidazole is at least equally effective. 

Metronidazole is used for treatment of bovine trichomoniasis by topical application or intravenous injection of 75 mg/kg bw. It is also used for treatment of swine dysentery at a dosage of 25 mg/kg bw/day for 4 days, whereas, for eradication of the disease in herds, treatment for 7 days followed, after 3-4 weeks, by a second treatment for 5 days in indicated. Metronidazole is a genotoxic carcinogen in animals. 

Residue depletion studies are very limited for metronidazole. After intrauterine treatment of cows with metronidazole at the recommended dosage, residues of metronidazole and its main metabolite hydroxymetronidazole could be detected in the milk collected at 2 and 6 h after dosing residues declined to below the limit of detection at 43 h postdosing. 

P. P. Pashankov and L. L. Kostova, Reversed-phase high-performance liquid chromatography of metronidazole benzoate in suspension dosage form, J. Chromatogr., 394 382 (1987). 

High-performance liquid chromatography (HPLC) has been used to analyze metronidazole [1435-1437], misonidazole [1309,1438], and other nitroimidazoles [1435, 1439] in body fluids or pharmaceutical dosage forms. HPLC analysis of effect of hypoxic-cell radiosensitizer misonidazole on the radiation-induced reduction of DNA bases (thymine, cytosine, and adenine) has been carried out [1440, 1441], HPLC was employed to characterize different nitroimidazoles [327, 366, 388,409, 450, 1442-1444], nitropyrazoles [246, 301], nitrothiazoles [366], l-aryl(hetaryl)-4-nitro-l,2,3-triazoles [601], nitrobenzimidazoles [707], nitrobenzofurazans [774, 1445-1449], nitrobenzotriazoles [1450],... 

Acid-base titration method was employed for quantitative determination of metronidazole in pharmaceutical dosage forms and compared with the other methods... 

Metronidazole Up to 99% of the intestinal anaerobes that are largely responsible for the bacterial formation of ammonia are affected by metronizadole. Its efficacy corresponds to that of neomycin and paromomycin. The mode of action is still unresolved. The dosage is 3(-4) X 0.4 g/day with subsequent reduction to 2 x 0.4 g/day provided two or three stools can be produced each day. When used for longer periods, peripheral neuropathies can occur. For this reason, initial treatment with metronidazole should be replaced as soon as possible by long-term lactulose therapy. (147)... 

The administration of lactulose over an extended period of time (dosage aim = 2-3 stools per day) is recommended. (858) It is advisable to use a combination with metronidazole or with non-absorbable antibiotics (e. g. paramomycine) preoperatively in order to suppress the gram-negative intestinal flora and thus also the formation of endotoxins. If necessary, antimycotics may be administered in addition. 

Metronidazole Potentiation (195) Stereoselective inhibition of metabolism (warfarin) (195) Adjust dosage... 

An unusual Antabuse-type reaction reported on one occasion seems to have been due to an interaction of metronidazole with the alcohol present in the high-dosage form X-Prep (SEDA-15, 398). 

Martino PD. Censi R, Malaj L. et al. Influence of metronidazole particle properties on granules prepared in a high-.shear mixer-granulator. Drug Dev Ind Pharm 2(X)7 33(2) 121-31. Lantz RJ. Size reduction. In Licberman HA, Schwartz JB, eds. Pharmaceutical Dosage Forms, 2nd ed. Vol. 2. New York Marcel Dekker, Inc., 1990 107-2(X). 

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