{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:22:39Z","timestamp":1762867359357,"version":"3.41.2"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T00:00:00Z","timestamp":1517961600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fosfomycin has emerged as a potential therapy for multidrug\u2010resistant bacterial infections. In most European countries, the oral formulation is only approved as a 3\u00a0g single dose for treatment of uncomplicated cystitis. However, for the treatment of complicated systemic infections, this dose regimen is unlikely to reach efficacious serum and tissue concentrations. This study aims to investigate different fosfomycin\u2010dosing regimens to evaluate its rationale for treatment of systemic infections. Serum concentration\u2010time profiles of fosfomycin were simulated using a population pharmacokinetic model based on published pharmacokinetic parameter values, their uncertainty, inter\u2010individual variability and covariates. The model was validated on published data and used to simulate a wide range of dosing regimens for oral and intravenous administration of fosfomycin. Finally, based on the minimum inhibitory concentration for <jats:italic>E.\u00a0coli<\/jats:italic>, surrogate pharmacodynamic indices were calculated for each dosing regimen. This is the first population pharmacokinetic model to describe the oral pharmacokinetics of fosfomycin using data from different literature sources. The model and surrogate pharmacodynamic indices provide quantitative evidence that a dosing regimen of 6\u201312\u00a0g per day divided in 3 doses is required to obtain efficacious exposure and may serve as a first step in the treatment of systemic multi\u2010drug\u2010resistant bacterial infections.<\/jats:p>","DOI":"10.1002\/prp2.378","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T05:02:39Z","timestamp":1517979759000},"source":"Crossref","is-referenced-by-count":12,"title":["Fosfomycin as a potential therapy for the treatment of systemic infections: a population pharmacokinetic model to simulate multiple dosing regimens"],"prefix":"10.1002","volume":"6","author":[{"given":"Natalia V.","family":"Ortiz Zacar\u00edas","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneke C.","family":"Dijkmans","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"},{"name":"Department of Medical Microbiology Medical Center Haaglanden The Hague the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacobus","family":"Burggraaf","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology Radboud University Nijmegen Medical Center Nijmegen the Netherlands"},{"name":"Department of Microbiology and Infectious Diseases Erasmus MC Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik B.","family":"Wilms","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy The Hague Hospitals The Hague the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cees","family":"van Nieuwkoop","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine The Hague Hospitals The Hague the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"University Groningen University Medical Center Groningen Department of Clinical Pharmacy and Pharmacology Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid M. C.","family":"Kamerling","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-9008","authenticated-orcid":false,"given":"Jasper","family":"Stevens","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"},{"name":"University Groningen University Medical Center Groningen Department of Clinical Pharmacy and Pharmacology Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,7]]},"reference":[{"volume-title":"Priority Medicines for Europe and the World","year":"2004","author":"Kaplan W","key":"e_1_2_6_2_1"},{"volume-title":"Priority medicines for Europe and the world \u2010 2013 update","year":"2013","author":"Kaplan W","key":"e_1_2_6_3_1"},{"key":"e_1_2_6_4_1","unstructured":"World Health Organization.Antibiotic Resistance: Multi\u2010Country Public Awareness Survey.2015."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70318-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2011.02.003"},{"volume-title":"The Bacterial Challenge: Time to React","year":"2009","author":"ECDC\/EMEA","key":"e_1_2_6_7_1"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2693"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e328358afe5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.166.3901.122"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1974.tb43277.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/527442"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/35.1.228"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70325-1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.10.019"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-007-0456-4"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.03.009"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02921.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2011.616221"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-009-0833-2"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1157\/13093873","article-title":"Fosfomicina trometamol. Dosis m\u00faltiples como pauta larga en el tratamiento de las infecciones urinarias bajas","volume":"24","author":"S\u00e1daba\u2010D\u00edaz De Rada B","year":"2006","journal-title":"Enferm Infecc Microbiol Clin"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004157"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600600504"},{"issue":"1","key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000472864","article-title":"Pharmacokinetic profile of fosfomycin trometamol (Monuril)","volume":"13","author":"Segre G","year":"1987","journal-title":"Eur Urol"},{"key":"e_1_2_6_26_1","unstructured":"KjellssonM KernS SauermannR DartoisV PillaiG.Modeling the permeability of fosfomycin into abscess fluid. In: PAGE 18 (2009) Abstr 1574 .2009. [www.page-meeting.org\/?abstract=1574]."},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01321-15"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.5"},{"key":"e_1_2_6_29_1","unstructured":"European Committee on Antimicrobial Susceptibility Testing.Fosfomycin: Rationale for the clinical breakpoints version 1.0.2013."},{"key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/BF01640831","article-title":"Fosfomycin\u2010Konzentrationen im Serum und in der Galle","volume":"10","author":"M\u00fcller O","year":"1982","journal-title":"Infection"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000238809"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9485-1"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.11.4448-4454.2005"},{"volume-title":"R: a language and environment for statistical computing","year":"2010","author":"R Development Core Team","key":"e_1_2_6_34_1"},{"key":"e_1_2_6_35_1","first-page":"35","volume-title":"RStudio: integrated Development for R","author":"R Studio Team","year":"2012"},{"issue":"1","key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1159\/000222043","article-title":"Pharmacokinetic study of fosfomycin and its bioavailability","volume":"23","author":"Cadorniga R","year":"1977","journal-title":"Chemotherapy"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki079"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu580"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh158"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg187"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2006.05.019"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-009-7108-9"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03099-15"},{"key":"e_1_2_6_44_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijid.2016.06.017","article-title":"Optimizing intravenous fosfomycin dosing in combination with carbapenems for treatment of Pseudomonas aeruginosa infections in critically ill patients based on pharmacokinetic\/pharmacodynamic (PK\/PD) simulation","volume":"50","author":"Asuphon O","year":"2016","journal-title":"Int J Infect Dis"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb1978.15.481"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.378","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.378","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T10:22:47Z","timestamp":1695723767000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1002\/prp2.378"],"URL":"https:\/\/doi.org\/10.1002\/prp2.378","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"type":"print","value":"2052-1707"},{"type":"electronic","value":"2052-1707"}],"subject":[],"published":{"date-parts":[[2018,2]]},"article-number":"e00378"}}