{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:13:26Z","timestamp":1760148806036,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship"},{"name":"90th Anniversary Chulalongkorn University Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Fosfomycin is a broad-spectrum, bactericidal antibiotic with low toxicity. It has been used in human medicine and is a promising candidate for treating infections in veterinary medicine. Different Fosfomycin salts exhibit various degrees of bioavailability. Tromethamine salt is the most commonly used oral form due to its improved bioavailability. However, information regarding its use with dogs is limited. Therefore, this study aimed to investigate the pharmacokinetics of oral Fosfomycin tromethamine in canine plasma and urine using liquid chromatography tandem mass spectrometry (LC-MS\/MS). Six healthy male beagles underwent a three-period three-treatment study: treatment 1 and 2 with single oral Fosfomycin tromethamine at 40 and 80 mg\/kg (the total doses with tromethamine salt were 75 and 150 mg\/kg, respectively), and treatment 3 with intravenously Fosfomycin disodium at 57 mg\/kg (the total dose with disodium salt was 75 mg\/kg). Dogs receiving oral Fosfomycin tromethamine at 75 and 150 mg\/kg, maximal drug concentration (Cmax) in plasma produced results of 34.46 \u00b1 12.52 and 66.40 \u00b1 12.64 \u00b5g\/mL, oral bioavailability (F) was approximately 38 and 45%, while urine Cmax was 4463.07 \u00b1 2208.88 and 8784.93 \u00b1 2303.46 \u00b5g\/mL, respectively. No serious adverse effects were reported, except loose stool in some dogs. The tremendously high urine Fosfomycin concentrations indicate that oral Fosfomycin tromethamine is suitable as an alternative treatment for bacterial cystitis in dogs.<\/jats:p>","DOI":"10.3390\/vetsci10060391","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:03:18Z","timestamp":1686276198000},"page":"391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Plasma and Urine Pharmacokinetics of Oral Fosfomycin Tromethamine in Dogs"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0363-2470","authenticated-orcid":false,"given":"Nattha","family":"Jariyapamornkoon","sequence":"first","affiliation":[{"name":"Graduate Program in Veterinary Bioscience, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koranis","family":"Patthanachai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nipattra","family":"Suanpairintr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1126\/science.166.3901.122","article-title":"Phosphonomycin, a new antibiotic produced by strains of streptomyces","volume":"166","author":"Hendlin","year":"1969","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3390\/antibiotics2020217","article-title":"Molecular Mechanisms and Clinical Impact of Acquired and Intrinsic Fosfomycin Resistance","volume":"2","author":"Blazquez","year":"2013","journal-title":"Antibiotics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1749-6632.1974.tb43277.x","article-title":"The mechanism of action of fosfomycin (phosphonomycin)","volume":"235","author":"Kahan","year":"1974","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1128\/jb.177.14.4194-4197.1995","article-title":"MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli","volume":"177","author":"Brown","year":"1995","journal-title":"J. Bacteriol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/jac\/35.1.228","article-title":"Antibacterial spectrum of fosfomycin trometamol","volume":"35","author":"Barry","year":"1995","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1128\/AAC.00349-11","article-title":"Antimicrobial susceptibilities of commonly encountered bacterial isolates to fosfomycin determined by agar dilution and disk diffusion methods","volume":"55","author":"Lu","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"961","DOI":"10.2217\/fmb.10.47","article-title":"Antimicrobial susceptibility of Gram-negative nonurinary bacteria to fosfomycin and other antimicrobials","volume":"5","author":"Samonis","year":"2010","journal-title":"Future Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1128\/CMR.00068-15","article-title":"Fosfomycin","volume":"29","author":"Falagas","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1473-3099(09)70325-1","article-title":"Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: A systematic review","volume":"10","author":"Falagas","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.vetmic.2010.10.025","article-title":"In vitro susceptibility of canine and feline Escherichia coli to fosfomycin","volume":"149","author":"Hubka","year":"2011","journal-title":"Vet. Microbiol."},{"key":"ref_11","unstructured":"Boothe, D.M. (2012). Small Animal Clinical Pharmacology & Therapeutics, Elsevier Saunders. [2nd ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1159\/000222043","article-title":"Pharmacokinetic study of fosfomycin and its bioavailability","volume":"23","author":"Cadorniga","year":"1977","journal-title":"Chemotherapy"},{"key":"ref_13","unstructured":"Frimodt-Moller (2010). Kucers\u2019 the Use of Antibiotics, Edward Arnold Ltd.. [6th ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-5173(80)90024-1","article-title":"Acid-catalyzed hydrolysis of fosfomycin and its implication in oral absorption of the drug","volume":"6","author":"Bundgaard","year":"1980","journal-title":"Int. J. Pharm."},{"key":"ref_15","first-page":"481","article-title":"Mechanisms of intestinal absorption of the antibiotic, fosfomycin, in brush-border membrane vesicles in rabbits and humans","volume":"15","author":"Ishizawa","year":"1992","journal-title":"J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dijkmans, A.C., Zacarias, N.V.O., Burggraaf, J., Mouton, J.W., Wilms, E.B., van Nieuwkoop, C., Touw, D.J., Stevens, J., and Kamerling, I.M.C. (2017). Fosfomycin: Pharmacological, Clinical and Future Perspectives. Antibiotics, 6.","DOI":"10.3390\/antibiotics6040024"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1159\/000239140","article-title":"Pharmacokinetic profile of fosfomycin trometamol","volume":"39","author":"Bergan","year":"1993","journal-title":"Chemotherapy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000472864","article-title":"Pharmacokinetic profile of fosfomycin trometamol (Monuril)","volume":"13","author":"Segre","year":"1987","journal-title":"Eur. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wenzler, E., Bleasdale, S.C., Sikka, M., Bunnell, K.L., Finnemeyer, M., Rosenkranz, S.L., Danziger, L.H., Rodvold, K.A., and Antibacterial Resistance Leadership Group (2018). Phase I Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.00464-18"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.rvsc.2007.08.011","article-title":"Pharmacokinetics of disodium-fosfomycin in mongrel dogs","volume":"85","author":"Gutierrez","year":"2008","journal-title":"Res. Vet. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000222040","article-title":"Pharmacokinetics of fosfomycin","volume":"23","author":"Kirby","year":"1977","journal-title":"Chemotherapy"},{"key":"ref_22","first-page":"26","article-title":"Fosfomycin: Uses and potentialities in veterinary medicine","volume":"4","author":"Perez","year":"2014","journal-title":"Open Vet. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1007\/BF01643430","article-title":"Degree of absorption, pharmacokinetics of fosfomycin trometamol and duration of urinary antibacterial activity","volume":"18","author":"Bergan","year":"1990","journal-title":"Infection"},{"key":"ref_24","unstructured":"EMA (2023, March 01). fosfomycin-article-31-referral-annex-iii_en. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/referral\/fosfomycin-article-31-referral-annex-iii_en.pdf."},{"key":"ref_25","unstructured":"USFDA (2023, March 01). MONUROL (Fosfomycin Tromethamine) Sachet, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2008\/050717s005lbl.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Silver, L.L. (2017). Fosfomycin: Mechanism and Resistance. Cold Spring Harb. Perspect. Med., 7.","DOI":"10.1101\/cshperspect.a025262"},{"key":"ref_27","unstructured":"Plumb, D.C. (2018). Plumb\u2019s Veterinary Drug Handbook, PhrmaVet Inc.. [9th ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Boothe, D., and Hubka, P. (2011). Pharmacokinetics and time dependent killing of fosfomycin in multi drug resistant-Escherichia coli urinary tract infections in dogs. Research Abstract Program of the 2011 ACVIM Forum Denver, Colorado, June 15\u201318, 2011. J. Vet. Intern. Med., 25.","DOI":"10.1111\/j.1939-1676.2011.00832.x"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2165\/00003495-199753040-00007","article-title":"Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections","volume":"53","author":"Patel","year":"1997","journal-title":"Drugs"},{"key":"ref_30","unstructured":"WHO (2023, March 01). Critically Important Antimicrobials for Human Medicine. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/312266\/9789241515528-eng.pdf."},{"key":"ref_31","unstructured":"EMA (2023, March 01). Categorisation of Antibiotics in the European Union. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/report\/categorisation-antibiotics-european-union-answer-request-european-commission-updating-scientific_en.pdf."},{"key":"ref_32","unstructured":"EMA (2023, March 01). Antimicrobial Advice Ad Hoc Expert Group. Available online: https:\/\/www.ema.europa.eu\/en\/committees\/working-parties-other-groups\/cvmp\/antimicrobial-advice-ad-hoc-expert-group-ameg."},{"key":"ref_33","unstructured":"Papich, M.G. (2016). Saunders Handbook of Veterinary Drugs: Small and Large Animal, Elsevier. [4th ed.]."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Harada, K., Shimizu, T., Kawaguchi, K., Furuhashi, T., and Ishihara, G. (2020). Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum beta-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study. Antibiotics, 9.","DOI":"10.3390\/antibiotics9050230"},{"key":"ref_35","unstructured":"USFDA (2023, March 01). Bioanalytical Method Validation, Available online: https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf."},{"key":"ref_36","unstructured":"EMA (2023, March 01). Guideline on Bioanalytical Method Validation. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-bioanalytical-method-validation_en.pdf."},{"key":"ref_37","first-page":"424","article-title":"Pharmacokinetics and bioavailability of calcium fosfomycin in post weaning piglets after oral administration","volume":"6","author":"Soraci","year":"2012","journal-title":"Int. J. Agro Vet. Med. Sci."},{"key":"ref_38","first-page":"107","article-title":"Fosfomycin distribution in the lower urinary tract after administration of fosfomycin trometamol salt","volume":"14","author":"Scaglione","year":"1994","journal-title":"Int. J. Clin. Pharm. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1159\/000222042","article-title":"Fosfomycin: Absorption and excretion","volume":"23","author":"Shimizu","year":"1977","journal-title":"Chemotherapy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5691","DOI":"10.1021\/acs.jmedchem.5b00201","article-title":"Volume of Distribution in Drug Design","volume":"58","author":"Smith","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_41","unstructured":"Elliott, J., and Grauer, G.F. (2007). BSAVA Manual of Canine and Feline Nephrology and Urology, Blackwell Publishing. [2nd ed.]."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wenzler, E., Ellis-Grosse, E.J., and Rodvold, K.A. (2017). Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00775-17"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1093\/jac\/dkaa294","article-title":"Pharmacokinetics of fosfomycin in patients with prophylactic treatment for recurrent Escherichia coli urinary tract infection","volume":"75","author":"Kuiper","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Abbott, I.J., van Gorp, E., Wijma, R.A., Meletiadis, J., Roberts, J.A., Mouton, J.W., and Peleg, A.Y. (2020). Oral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against Enterobacterales: The Importance of Heteroresistance for Growth Outcome. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.01982-19"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jchromb.2017.07.036","article-title":"A fast and sensitive LC-MS\/MS method for the quantification of fosfomycin in human urine and plasma using one sample preparation method and HILIC chromatography","volume":"1061\u20131062","author":"Wijma","year":"2017","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0034-5288(02)00039-5","article-title":"The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics","volume":"73","author":"Toutain","year":"2002","journal-title":"Res. Vet. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lepak, A.J., Zhao, M., VanScoy, B., Taylor, D.S., Ellis-Grosse, E., Ambrose, P.G., and Andes, D.R. (2017). In Vivo Pharmacokinetics and Pharmacodynamics of ZTI-01 (Fosfomycin for Injection) in the Neutropenic Murine Thigh Infection Model against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00476-17"},{"key":"ref_48","unstructured":"CLSI (2021). Performance Standards for Antimicrobial Susceptibility Testing, CLSI. [31st ed.]. CLSI Supplement M100."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fedrigo, N.H., Mazucheli, J., Albiero, J., Shinohara, D.R., Lodi, F.G., Machado, A., Sy, S.K.B., and Tognim, M.C.B. (2017). Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.02498-16"}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/10\/6\/391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:50:56Z","timestamp":1760125856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/10\/6\/391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,8]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["vetsci10060391"],"URL":"https:\/\/doi.org\/10.3390\/vetsci10060391","relation":{},"ISSN":["2306-7381"],"issn-type":[{"type":"electronic","value":"2306-7381"}],"subject":[],"published":{"date-parts":[[2023,6,8]]}}}