{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:18:45Z","timestamp":1787501925225,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Spero Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tebipenem pivoxil hydrobromide is a novel oral carbapenem prodrug of tebipenem, the active moiety. We assessed tebipenem steady-state pharmacokinetics in the skin and soft tissue in healthy subjects and infected patients with diabetes using in vivo microdialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six healthy subjects and six patients with an ongoing diabetic foot infection (DFI) received tebipenem pivoxil hydrobromide 600\u2005mg orally every 8\u2005h for three doses. A microdialysis probe was inserted in the thigh of healthy subjects or by the wound margin in patients. Plasma and dialysate samples were obtained immediately prior to the third dose and sampled over 8\u2005h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tebipenem plasma protein binding (mean\u200a\u00b1\u200aSD) was 50.2%\u200a\u00b1\u200a2.4% in healthy subjects and 53.5%\u200a\u00b1\u200a5.6% in infected patients. Mean\u200a\u00b1\u200aSD tebipenem pharmacokinetic parameters in plasma for healthy subjects and infected patients were: maximum free concentration (fCmax), 3.74\u200a\u00b1\u200a2.35 and 3.40\u200a\u00b1\u200a2.86\u2005mg\/L, respectively; half-life, 0.88\u200a\u00b1\u200a0.11 and 2.02\u200a\u00b1\u200a1.32\u2005h; fAUC0\u20138, 5.61\u200a\u00b1\u200a1.64 and 10.01\u200a\u00b1\u200a4.81\u2005mg\u00b7h\/L. Tebipenem tissue AUC0\u20138 was 5.99\u200a\u00b1\u200a3.07 and 8.60\u200a\u00b1\u200a2.88\u2005mg\u00b7h\/L for healthy subjects and patients, respectively. The interstitial concentration\u2013time profile largely mirrored the free plasma profile within both populations, resulting in a penetration ratio of 107% in healthy subjects and 90% in infected patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tebipenem demonstrated excellent distribution into skin and soft tissue of healthy subjects and patients with DFI following oral administration of 600\u2005mg of tebipenem pivoxil hydrobromide.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkac399","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T11:12:02Z","timestamp":1667387522000},"page":"296-301","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacokinetics and soft-tissue distribution of tebipenem pivoxil hydrobromide using microdialysis: a study in healthy subjects and patients with diabetic foot infections"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-3263","authenticated-orcid":false,"given":"Yasmeen","family":"Abouelhassan","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Fratoni","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley K","family":"Shepard","sequence":"additional","affiliation":[{"name":"Hartford Healthcare Medical Group, Podiatric Surgery , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4148-0165","authenticated-orcid":false,"given":"David P","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"},{"name":"Division of Infectious Diseases, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-0924","authenticated-orcid":false,"given":"Tomefa E","family":"Asempa","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital , Hartford, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"2023010801152745200_dkac399-B1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1186\/s12879-021-06516-7","article-title":"The microbiology of diabetic foot infections: a meta-analysis","volume":"21","author":"Macdonald","year":"2021","journal-title":"BMC Infect Dis"},{"key":"2023010801152745200_dkac399-B2","doi-asserted-by":"crossref","DOI":"10.1590\/0100-6991e-20202471","article-title":"Microbiologic characteristics and antibiotic resistance rates of diabetic foot infections","volume":"47","author":"Pontes","year":"2020","journal-title":"Rev Col Bras Cir"},{"key":"2023010801152745200_dkac399-B3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.7547\/1030002","article-title":"2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections","volume":"103","author":"Lipsky","year":"2013","journal-title":"J Am Podiatr Med Assoc"},{"key":"2023010801152745200_dkac399-B4","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/phar.2614","article-title":"Tebipenem pivoxil hydrobromide\u2014no PICC, no problem!","volume":"41","author":"Sodhi","year":"2021","journal-title":"Pharmacotherapy"},{"key":"2023010801152745200_dkac399-B5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1080\/14787210.2018.1496821","article-title":"Tebipenem, the first oral carbapenem antibiotic","volume":"16","author":"Jain","year":"2018","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2023010801152745200_dkac399-B6","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00603-19","article-title":"Pharmacodynamics of tebipenem: new options for oral treatment of multidrug-resistant Gram-negative infections","volume":"63","author":"McEntee","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B7","doi-asserted-by":"crossref","first-page":"E600\u20138","DOI":"10.1208\/aapsj070362","article-title":"Lung microdialysis\u2014a powerful tool for the determination of exogenous and endogenous compounds in the lower respiratory tract (mini-review)","volume":"7","author":"Zeitlinger","year":"2005","journal-title":"AAPS J"},{"key":"2023010801152745200_dkac399-B8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1208\/s12248-016-0020-1","article-title":"Utility of microdialysis in infectious disease drug development and dose optimization","volume":"19","author":"Deitchman","year":"2017","journal-title":"AAPS J"},{"key":"2023010801152745200_dkac399-B9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ijantimicag.2010.08.013","article-title":"Antimicrobial chemotherapy and lung microdialysis: a review","volume":"36","author":"Dhanani","year":"2010","journal-title":"Int J Antimicrob Agents"},{"key":"2023010801152745200_dkac399-B10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0160-5402(89)90011-9","article-title":"Intracerebral microdialysis: I. Experimental studies of diffusion kinetics","volume":"22","author":"Lindefors","year":"1989","journal-title":"J Pharmacol Methods"},{"key":"2023010801152745200_dkac399-B11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13601-019-0262-y","article-title":"Skin microdialysis: methods, applications and future opportunities\u2014an EAACI position paper","volume":"9","author":"Baumann","year":"2019","journal-title":"Clin Transl Allergy"},{"key":"2023010801152745200_dkac399-B12","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/00007691-199602000-00003","article-title":"Monitoring free extracellular valproic acid by microdialysis in epileptic patients","volume":"18","author":"Stahle","year":"1996","journal-title":"Ther Drug Monit"},{"key":"2023010801152745200_dkac399-B13","doi-asserted-by":"crossref","first-page":"e00483","DOI":"10.1002\/prp2.483","article-title":"In vitro evaluation of an intravenous microdialysis catheter for therapeutic drug monitoring of gentamicin and vancomycin","volume":"7","author":"van der Mast","year":"2019","journal-title":"Pharmacol Res Perspect"},{"key":"2023010801152745200_dkac399-B14","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1093\/jac\/dkac055","article-title":"Omadacycline pharmacokinetics and soft-tissue penetration in diabetic patients with wound infections and healthy volunteers using in vivo microdialysis","volume":"77","author":"Gill","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2023010801152745200_dkac399-B15","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01880-17","article-title":"Comparative assessment of tedizolid pharmacokinetics and tissue penetration between diabetic patients with wound infections and healthy volunteers via in vivo microdialysis","volume":"62","author":"Stainton","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B16","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1128\/AAC.00589-08","article-title":"In vivo microdialysis study of the penetration of daptomycin into soft tissues in diabetic versus healthy volunteers","volume":"52","author":"Kim","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B17","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1128\/AAC.01051-10","article-title":"Tissue penetration and pharmacokinetics of tigecycline in diabetic patients with chronic wound infections described by using in vivo microdialysis","volume":"54","author":"Bulik","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B18","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.1128\/AAC.00445-11","article-title":"Determination of tissue penetration and pharmacokinetics of linezolid in patients with diabetic foot infections using in vivo microdialysis","volume":"55","author":"Wiskirchen","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B19","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01564-21","article-title":"Target site pharmacokinetics of meropenem: measurement in human explanted lung tissue by bronchoalveolar lavage, microdialysis, and homogenized lung tissue","volume":"65","author":"Paal","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B20","first-page":"97","article-title":"In vitro microdialysis membrane efficiency of broad-spectrum antibiotics in combination and alone","volume":"6","author":"MacVane","year":"2014","journal-title":"Clin Pharmacol"},{"key":"2023010801152745200_dkac399-B21","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1177\/0091270006299091","article-title":"AAPS-FDA Workshop white paper: microdialysis principles, application, and regulatory perspectives","volume":"47","author":"Chaurasia","year":"2007","journal-title":"J Clin Pharmacol"},{"key":"2023010801152745200_dkac399-B22","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00618-19","article-title":"Safety, pharmacokinetics, and food effect of tebipenem pivoxil hydrobromide after single and multiple ascending oral doses in healthy adult subjects","volume":"63","author":"Eckburg","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B23","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02618-18","article-title":"Antimicrobial activity evaluation of tebipenem (SPR859), an orally available carbapenem, against a global set of Enterobacteriaceae isolates, including a challenge set of organisms","volume":"63","author":"Arends","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010801152745200_dkac399-B24","first-page":"1","article-title":"Treatment of patients with diabetic gastroparesis","volume":"6","author":"Parkman","year":"2010","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"2023010801152745200_dkac399-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13300-018-0454-9","article-title":"Diabetic gastroparesis: principles and current trends in management","volume":"9","author":"Krishnasamy","year":"2018","journal-title":"Diabetes Ther"},{"key":"2023010801152745200_dkac399-B26","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4239\/wjd.v1.i2.48","article-title":"Renal function in diabetic nephropathy","volume":"1","author":"Dabla","year":"2010","journal-title":"World J Diabetes"},{"key":"2023010801152745200_dkac399-B27","doi-asserted-by":"crossref","DOI":"10.1128\/aac.02407-21","article-title":"Pharmacokinetics of oral tebipenem pivoxil hydrobromide in subjects with various degrees of renal impairment","volume":"66","author":"Patel","year":"2022","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/1\/296\/48444496\/dkac399.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/1\/296\/48444496\/dkac399.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T20:16:21Z","timestamp":1673122581000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/1\/296\/6845774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,25]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,11,25]]},"published-print":{"date-parts":[[2023,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkac399","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,5]]},"published":{"date-parts":[[2022,11,25]]}}}