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Clinical Pharmacokinetics May 1999Metronidazole, the prototype nitroimidazole antimicrobial, was originally introduced to treat Trichomonas vaginalis, but is now used for the treatment of anaerobic and... (Review)
Review
Metronidazole, the prototype nitroimidazole antimicrobial, was originally introduced to treat Trichomonas vaginalis, but is now used for the treatment of anaerobic and protozoal infections. The nitroimidazoles are bactericidal through toxic metabolites which cause DNA strand breakage. Resistance, both clinical and microbiological, has been described only rarely. Metronidazole given orally is absorbed almost completely, with bioavailability > 90% for tablets; absorption is unaffected by infection. Rectal and intravaginal absorption are 67 to 82%, and 20 to 56%, of the dose, respectively. Metronidazole is distributed widely and has low protein binding (< 20%). The volume of distribution at steady state in adults is 0.51 to 1.1 L/kg. Metronidazole reaches 60 to 100% of plasma concentrations in most tissues studied, including the central nervous system, but does not reach high concentrations in placental tissue. Metronidazole is extensively metabolised by the liver to 5 metabolites. The hydroxy metabolite has biological activity of 30 to 65% and a longer elimination half-life than the parent compound. The majority of metronidazole and its metabolites are excreted in urine and faeces, with less than 12% excreted unchanged in urine. The pharmacokinetics of metronidazole are unaffected by acute or chronic renal failure, haemodialysis, continuous ambulatory peritoneal dialysis, age, pregnancy or enteric disease. Renal dysfunction reduces the elimination of metronidazole metabolites; however, no toxicity has been documented and dosage alterations are unnecessary. Liver disease leads to a decreased clearance of metronidazole and dosage reduction is recommended. Recent pharmacodynamic studies of metronidazole have demonstrated activity for 12 to 24 hours after administration of metronidazole 1 g. The post-antibiotic effect of metronidazole extends beyond 3 hours after the concentration falls below the minimum inhibitory concentration (MIC). The concentration-dependent bactericidal activity, prolonged half-life and sustained activity in plasma support the clinical evaluation of higher doses of metronidazole given less frequently. Metronidazole-containing regimens for Helicobacter pylori in combination with proton pump inhibitors demonstrate higher success rates than antimicrobial regimens alone. The pharmacokinetics of metronidazole in gastric fluid appear contradictory to these results, since omeprazole reduces peak drug concentration and area under the concentration-time curve for metronidazole and its hydroxy metabolite; however, concentrations remain above the MIC. Other members of this class include tinidazole, ornidazole and secnidazole. They are also well absorbed and distributed after oral administration. Their only distinguishing features are prolonged half-lives compared with metronidazole. The choice of nitroimidazole may be influenced by the longer administration intervals possible with other members of this class; however, metronidazole remains the predominant antimicrobial for anaerobic and protozoal infections.
Topics: Adult; Aged; Anti-Infective Agents; Antitrichomonal Agents; Area Under Curve; Biological Availability; Dosage Forms; Drug Interactions; Female; Half-Life; Humans; Intestinal Absorption; Metronidazole; Middle Aged; Nitroimidazoles; Pregnancy; Protozoan Infections; Tissue Distribution
PubMed: 10384859
DOI: 10.2165/00003088-199936050-00004 -
Bioorganic & Medicinal Chemistry Aug 2017The 7-benzylidenenaltrexone (BNTX) derivatives 2a-v, 3a-c, 13a-c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The...
The 7-benzylidenenaltrexone (BNTX) derivatives 2a-v, 3a-c, 13a-c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC=10.5µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents. In addition, the mechanism of the antitrichomonal activity of the BNTX derivatives may differ from that of the standard drug, metronidazole.
Topics: Animals; Antitrichomonal Agents; Benzylidene Compounds; CHO Cells; Cricetulus; Dose-Response Relationship, Drug; Molecular Structure; Naltrexone; Receptors, Opioid, delta; Structure-Activity Relationship; Trichomonas vaginalis
PubMed: 28662966
DOI: 10.1016/j.bmc.2017.06.026 -
Revue Neurologique May 2018
Topics: Aged; Antitrichomonal Agents; Brain Diseases; Humans; Magnetic Resonance Imaging; Male; Metronidazole
PubMed: 29699775
DOI: 10.1016/j.neurol.2017.09.013 -
Clinical Microbiology Reviews Oct 2004Trichomoniasis is perhaps the most common curable sexually transmitted disease worldwide, yet few resources are devoted to its control. It is associated with potentially... (Review)
Review
Trichomoniasis is perhaps the most common curable sexually transmitted disease worldwide, yet few resources are devoted to its control. It is associated with potentially serious complications such as preterm birth and human immunodeficiency virus acquisition and transmission. The immunology of a related organism, Tritrichomonas foetus, which causes disease in cattle, has been investigated to some extent, but more work is needed for the human strain, Trichomonas vaginalis. In addition, although trichomoniasis is easily treated with oral metronidazole, there is concern that the number of strains resistant to this antibiotic are increasing, and currently no alternative is licensed in the United States. As more is appreciated concerning the important public health implications of this common infection, more work will need to be done in understanding the diagnosis, treatment, and immunology of this organism.
Topics: Animals; Antitrichomonal Agents; Female; Humans; Trichomonas Infections; Trichomonas vaginalis
PubMed: 15489349
DOI: 10.1128/CMR.17.4.794-803.2004 -
The Journal of Pharmacy and Pharmacology Oct 1961
Topics: Antitrichomonal Agents; Trichomonas
PubMed: 13917874
DOI: 10.1111/j.2042-7158.1961.tb11876.x -
Antitrichomonal activity of metronidazole-loaded lactoferrin nanoparticles in pigeon trichomoniasis.Parasitology Research Sep 2021In recent years, increasing attention has been paid to the novel drug delivery systems to reduce the dose of the drug and avoid side effects. Metronidazole has been used...
In recent years, increasing attention has been paid to the novel drug delivery systems to reduce the dose of the drug and avoid side effects. Metronidazole has been used for many years in the treatment of anaerobic bacterial and protozoal infections. Nanolactoferrin, a newly developed antibacterial agent originated from lactoferrin, is applied both as an active therapeutic and a drug nanocarrier. The present study describes the development and characterization of metronidazole-loaded lactoferrin nanoparticles (nano-MTZ) as well as reports their antitrichomonal activity on Trichomonas gallinae, the protozoal causative agent of pigeon trichomoniasis. The activity of the nano-MTZ is compared with the regular metronidazole formulation (MTZ) under in vitro and in vivo conditions. Additionally, cytotoxicity of the nano-MTZ to fibroblast cell line and possible hepatotoxicity in treated pigeons were evaluated. Nano-MTZ was prepared based on the thermal treatment method and the average size and surface charge of the dispersion were 30.6 nm and - 44.6 mv, respectively. No significant cytotoxicity was noted for the nano-MTZ in comparison to the MTZ. Loading efficiency in nano-MTZ was calculated as 55%. In vitro susceptibility results demonstrated 24 h 90% lethal concentration values of 4.23 and 6.64 µg/mL for MTZ and nano-MTZ, respectively. Oral treatment of the pigeons experimentally infected with T. gallinae resulted in the earlier eradication of the infection in the nano-MTZ-treated pigeons. No adverse effects on the liver function have been observed for the nano-MTZ. These findings suggest that nanolactoferrin is a promising platform for the development of novel MTZ formulations with improved antitrichomonal activity.
Topics: Animals; Antitrichomonal Agents; Columbidae; Lactoferrin; Metronidazole; Nanoparticles; Trichomonas Infections
PubMed: 34342682
DOI: 10.1007/s00436-021-07263-z -
Annals of Parasitology 2022In recent years, increasing attention has been paid in veterinary medicine to find novel natural resources to reduce the use of synthetic drugs, avoid side effects, and...
In recent years, increasing attention has been paid in veterinary medicine to find novel natural resources to reduce the use of synthetic drugs, avoid side effects, and for better compliance of the animals’ owners. Metronidazole has been used for many years in the treatment of birds’ trichomonosis. Carvacrol is a terpenoid and several biologic activities was attributed to it. The present study developed and characterized a carvacrol nanoemulsion (NanoCAV) and investigated its antitrichomonal activity on Trichomonas gallinae, the causative agent of pigeon trichomonosis, under in vitro condition and compared it with carvacrol (CAV) and the standard antitrichomonal dug, metronidazole (MTZ). Additionally, cytotoxicity of the developed formulation to the fibroblast cell line was evaluated. The NanoCAV mean size and surface charge were 80.5 nm and -31.2 mv, respectively. No significant cytotoxicity was observed for the NanoCAV. Incorporation efficiency of NanoCAV was measured as 75%. Results of antitrichomonal activity assay showed 12 h fifty percent lethal concentrations of 0.39 and 0.27 μg/ml for CAV and NanoCAV, respectively. The NanoCAV based on in vitro activity and low cytotoxicity, can be further studied for its efficacy and safety profile in the pigeons.
Topics: Animals; Antitrichomonal Agents; Bird Diseases; Columbidae; Cymenes; Metronidazole; Protamines; Trichomonas; Trichomonas Infections
PubMed: 35491905
DOI: 10.17420/ap6801.419 -
Drug and Therapeutics Bulletin Feb 1969
Topics: Antiprotozoal Agents; Antitrichomonal Agents; Female; Humans; Nitrofurantoin; Oxazoles; Pregnancy; Trichomonas Vaginitis
PubMed: 5770287
DOI: No ID Found -
Antitrichomonal activity and docking analysis of thiazole derivatives as TvMP50 protease inhibitors.Parasitology Research Jan 2021Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most prevalent non-viral sexually transmitted infection that affects over 170 million people...
Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most prevalent non-viral sexually transmitted infection that affects over 170 million people worldwide. The only type of drug recommended for the therapeutic control of trichomoniasis is the 5-nitroimidazoles, although there have been reports of some undesirable side effects and clinical resistance. Hence, the need for the search for new tricomonicidal agents is necessary. In a previous work, we demonstrated that two 2-amino-4-aryl thiazole derivatives (ATZ-1 and ATZ-2) possess a portent antigiardial effect. In the current paper, we investigated the in vitro antitrichomonal activity of these thiazole compounds. Both ATZ-1 and ATZ-2 reduced the viability and growth of parasites in a dose-dependent manner, with an IC value of 0.15 μg/mL and 0.18 μg/mL, respectively. Furthermore, both thiazole compounds were able to decrease the proteolytic activity in T. vaginalis trophozoites compared with untreated parasites. Interestingly, a full proteolytic inhibition profile was observed in the 50-kDa region which was associated with the decreased expression of the gene that codes for the trichomonad protease TvMP50. The docking simulations predicted strong interactions of the thiazole compounds in the TvMP50 protease's active site, suggesting a possible role as protease inhibitors. Our results demonstrate the potential of 2-amino-4-aryl thiazole derivatives as trichomonicidal compounds and could be, mechanistically, involved in the inhibition of key trichomonad proteases.
Topics: Antitrichomonal Agents; Humans; Parasitic Sensitivity Tests; Protease Inhibitors; Thiazoles; Trichomonas Infections; Trichomonas vaginalis
PubMed: 33073325
DOI: 10.1007/s00436-020-06931-w -
Acta Gastro-enterologica Belgica 2010
Topics: Antitrichomonal Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Liver Function Tests; Middle Aged; Ornidazole
PubMed: 20690574
DOI: No ID Found