{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T18:18:36Z","timestamp":1721499516460},"reference-count":26,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Sufficient antibiotic concentrations at the infection site are a prerequisite for good bacterial killing. This study was performed to determine pharmacokinetics of doripenem in soft tissues and saliva. Six healthy male volunteers received a single intravenous infusion of 500 mg doripenem over 1 h. The concentrations of doripenem were measured over 8 h in saliva, plasma, and extracellular space fluid of skeletal muscle and subcutaneous adipose tissue employing\n            <jats:italic>in vivo<\/jats:italic>\n            microdialysis. Unbound drug concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry. Maximum concentrations of doripenem were 15.3 \u00b1 6.0 mg\/liter in plasma, 9.9 \u00b1 2.3 mg\/liter in subcutaneous adipose tissue, 6.6 \u00b1 2.9 mg\/liter in skeletal muscle, and 0.5 \u00b1 0.2 mg\/liter in saliva. Areas under the concentration-time curve (AUC) from 0 to infinity were 26.3 \u00b1 10.1, 20.4 \u00b1 3.8, 12.8 \u00b1 3.0, and 1.0 \u00b1 0.5 mg \u00b7 h\/liter in plasma, adipose tissue, skeletal muscle, and saliva, respectively. Ratios of AUC in adipose tissue, skeletal muscle, and saliva to those in plasma were 0.84 \u00b1 0.28, 0.53 \u00b1 0.19, and 0.04 \u00b1 0.03, respectively. In all six volunteers, a threshold of \u226540% for \u201ctime above MIC,\u201d an index indicative of good antimicrobial activity, was exceeded in adipose tissue for MICs of \u22642 mg\/liter and in skeletal muscle for MICs \u22641.5 mg\/liter. Doripenem penetrates well into interstitial space fluid of skeletal muscle and adipose tissue, suggesting good antimicrobial activity in infected soft tissues, whereas it is detectable in relatively low concentrations in saliva.\n          <\/jats:p>","DOI":"10.1128\/aac.05506-11","type":"journal-article","created":{"date-parts":[[2011,11,15]],"date-time":"2011-11-15T19:06:06Z","timestamp":1321383966000},"page":"532-535","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Penetration of Doripenem into Skeletal Muscle and Subcutaneous Adipose Tissue in Healthy Volunteers"],"prefix":"10.1128","volume":"56","author":[{"given":"Bernhard","family":"Burian","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria"},{"name":"Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Zeitlinger","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Donath","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gottfried","family":"Reznicek","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sauermann","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2147\/DDDT.S3083","article-title":"Characteristics of doripenem: a new broad-spectrum antibiotic","volume":"3","author":"Alvarez-Lerma F","year":"2009","unstructured":"Alvarez-LermaF GrauS FerrandezO. 2009. Characteristics of doripenem: a new broad-spectrum antibiotic. Drug Des. Devel. Ther. 3:173\u2013190.","journal-title":"Drug Des. Devel. Ther"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s10096-010-0974-3","article-title":"Activity of doripenem against extended-spectrum beta-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates","volume":"29","author":"Betriu C","year":"2010","unstructured":"BetriuC. 2010. Activity of doripenem against extended-spectrum beta-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa isolates. Eur. J. Clin. Microbiol. Infect. Dis. 29:1179\u20131181.","journal-title":"Eur. J. Clin. Microbiol. Infect. 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