Pharmacokinetics metronidazole

The modest changes in the pharmacokinetics of tinidazole with cimetidine seem unlikely to be clinically significant, but bear them in mind in the case of an unexpected response to treatment. The interaction between metronidazole and cimetidine is not established, but any changes in metronidazole pharmacokinetics seem to be modest and unlikely to be important. 

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

Metabolism and pharmacokinetics of piprozolin were studied by RPC without prior clean-up of the urine sample (565). Misonidazole, metronidazole, and their metabolites have been analyzed using a ternary solvent system containing methanol-acetonitrile-5 mAf KH1PO4, pH 4, at volume ratios 4 3 93. The results facilitated the determination of the respective serum levels in a particular regimen of chemotherapy (364). The sig-... 

Many antimicrobial agents have similar pharmacokinetic properties when given orally or parenterally (ie, tetracyclines, trimethoprim-sulfamethoxazole, quinolones, chloramphenicol, metronidazole, clindamycin, rifampin, linezolid and fluconazole). In most cases, oral therapy with these drugs is equally effective, is less costly, and results in fewer complications than parenteral therapy. 

Iodoquinol (diiodohydroxyquin) is a halogenated hydroxy-quinoline. It is an effective luminal amebicide that is commonly used with metronidazole to treat amebic infections. Its pharmacokinetic properties are poorly understood. Ninety percent of the drug is retained in the intestine and excreted in the feces. The remainder enters the circulation, has a half-life of 11-14 hours, and is excreted in the urine as glucuronides. 

Pharmacokinetics. Metronidazole is well absorbed after oral or rectal administration and distributed to achieve sufficient concentration to eradicate infection in liver, gut wall and pelvic tissues. It is eliminated in the urine, partly imchanged and partly as metabolites. The t) is 8 h. 

Yacobi, A., Lai, Chii-Ming, and Levy, G, (1984). Pharmacokinetic and pharmacodynamic studies of acute interaction between Warfarin enantiomers and Metronidazol. /. Pharmacol Exp, Ther., 232 72-79,... 

Nilsson C, Aschan J, Hentschke P, Ringden O, Ljnngman P, Hassan M. The effect of metronidazole on bnsnlfan pharmacokinetics in patients nndergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 2003 31(6) 429-35. 

Bardakji Z, Jolivet J, Langelier Y, Besner JG, Ayoub J. 5-FluorouracU-metronidazole combination therapy in metastatic colorectal cancer. Clinical, pharmacokinetic and in vitro cytotoxicity studies. Cancer Chemother Pharmacol 1986 18(2) 140-4. 

Urtasun RC, Rabin HR, Partington J. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously. Surgery 1983 93(1 Pt 2) 145-8. 

Ralph ED. Clinical pharmacokinetics of metronidazole. Clin Pharmacokinet 1983 8(l) 43-62. 

Cooke CE, Sklar GE, Nappi JM. Possible pharmacokinetic interaction with quinidine ciprofloxacin or metronidazole Ann-Pharmacother 1996 30(4) 364-6. 

Pharmacokinetics of gentamicin in the horse. American Journal of Veterinary Research 41 351-354 Riviere J E 1999 Comparative pharmacokinetics principles, techniques and applications. Iowa State University Press, Ames, lA, pp. 47-61 Sp>echt T E, Brown M P, Qronwall R R et al 1992 Pharmacokinetics of metronidazole and its... 

Baggot, J.D., Wilson, W.D. Hietala, S. (1988b) Clinical pharmacokinetics of metronidazole in horses. Journal of Veterinary Pharmacology and Therapeutics, 11, 417-420. 

Pharmacokinetics Metronidazole is effective orally and is distributed widely to tissues, achieving CSF levels similar to those in the blood. The drug can also be given intravenously and is available in topical formulations. Elimination of metronidazole requires hepatic metabolism and dosage reduction may be needed in patients with liver dysfunction. 

Describe the pharmacodynamic and pharmacokinetic properties of the major amebicides tdilox-anide, emetine, iodoquinol, and metronidazole). List other clinical applications of metronidazole. Identify the drugs useful for prophylaxis and treatment of pneumocystosis and toxoplasmosis and know their toxic effects. 

Pharmacokinetics Metronidazole is effective orally and distributed widely to tissues. Elimination of the drug requires hepatic metabolism. 

Lau AH, Lam NP, Piscitelli SC, et al. Clinical pharmacokinetics of metronidazole anti-infectives. Clin Pharmacokinet 1992 23 328-364. 

Senkowsky BZ, et al, undated personal communication cited by Schwartz DE and Jeunet F, Comparative pharmacokinetic studies of ornidazole and metronidazole in man. Chemotherapy, 22, 19-29 (1976). 

Dykes, P.J., Hill, S., and Marks, R., 1997, Pharmacokinetics of topically applied metronidazol in two different formulations. Skin Pharmacol, 10, 28-33. 

There appear to be no clinically significant pharmacokinetic interactions between aztreonam and amikacin, cefradine, clindamycin, gentamicin, metronidazole or nafcillin. 

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). ... 

Because oral triple therapy to eradicate H. pylori using sucralfate instead of bismuth has yielded inconsistent results, a 5-day study was undertaken in 14 healthy subjects to investigate whether sucralfate interacts with metronidazole. It was found that sucralfate 2 g twice daily had no effect on the pharmacokinetics of a single 400-mg dose of metronidazole. Sucralfate would therefore not be expected to alter the effects of metronidazole. 

A study found that a single 400-mg oral dose of metronidazole had no effect on the pharmacokinetics of pefloxacin, and similarly pefloxacin did not affect the pharmacokinetics of metronidazole. In another study no interaetion was found between ciprofloxacin or ofloxacin (both 200 mg intravenously) and metronidazole 500 mg intravenously, and metronidazole with ciprofloxacin orally. ... 

Boeckh M, Grineisen S, Shokry F, Koej P, Brnier K, Krasemann C, Lode H Pharmacokinetics and serum bactericidal activity (SBA) of ciprofloxacin (CEP) and ofloxacin (OFL) alone and in combination with metronidazole (METRO) or chnd ycin (CLINDA). Intersci C( tfAnturncrob Agents Chem( ter( 9 28,246. 

One study found that the half-life of phenytoin was modestly prolonged by metronidazole, whereas another found no change in phenytoin pharmacokinetics. An anecdotal report describes a few patients who developed toxic phenytoin levels when given metronidazole. 

A pharmacokinetic study in 7 healthy subjects found that metronidazole 250 mg three times daily increased the half-life of a single 300-mg intravenous dose of phenytoin by about 40% (from 16 to 23 hours) and redueed the clearance by 15%. In contrast, another study in 5 healthy subjeets found that the pharmacokinetics of a single 300-mg oral dose of phenytoin were unaffected by metronidazole 400 mg twice daily for 6 days. An anecdotal report describes several patients (exact number not stated) who developed toxic phenytoin serum levels when given metronidazole. These appear to be the only reports of this potential interaction, and the reason for their discordant findings is not clear. It seems likely that few patients are likely to experience a clinieally significant interaction. 

A marked increase in fluorouracil toxicity was noted in 27 patients with metastatic colorectal cancer when they were given intravenous metronidazole 750 mg/m one hour before reeeiving intravenous fluorouracil 600 mg/m 5 days per week, every 4 weeks. Granuloeytopenia occurred in 74% of patients, nausea and vomiting in 48%, anaemia in 41%, stomatitis and oral ulceration in 34%, and thrombocytopenia in 19%. A pharmacokinetic study in 10 patients found that metronidazole reduced the clearance of fluorouracil by 27% over the 5-day period and increased the AUC by 34%. In vitro studies with human colon cancer cells failed to show any increased efficacy. ... 

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