{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:38:13Z","timestamp":1790915893666,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Daptomycin is a high\u2010use intravenous antimicrobial agent affording the convenience of once\u2010daily dosing. Prior studies suggest an opportunity to use a more operationally convenient fixed rather than weight\u2010based dosing but this approach has not been studied prospectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study quantified the probability of toxicity and efficacy end points by prospectively testing a fixed dose regimen of daptomycin (750\u2009mg) in obese and non\u2010obese adults. At least, three daptomycin concentrations were measured at steady\u2010state for each patient. A population pharmacokinetic model was constructed to evaluate concentration\u2010time profiles and investigate covariates of daptomycin clearance. Simulations were performed to evaluate the probability of achieving efficacy (24\u2010h area under the curve (AUC<jats:sub>0\u201024<\/jats:sub>)\u2009\u2265\u2009666\u2009mg\u2219h\/L) and toxicity (minimum concentration (<jats:italic>C<\/jats:italic>\n<jats:sub>min<\/jats:sub>) \u226524.3\u2009mg\/L) targets for fixed (500\u20131000\u2009mg) and weight\u2010based (6\u201312\u2009mg\/kg) daptomycin doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010one patients (16 females, 15 males) with median (interquartile range (IQR)) age of 50 (30, 62) years and weight of 74 (54, 156) kg were included in the final analysis. Fixed dose daptomycin (750\u2009mg) resulted in similar exposure across weights with a median (IQR) AUC<jats:sub>0\u201024<\/jats:sub> of 819 (499, 1501) mg\u2219h\/L and 749 (606, 1265) mg\u2219h\/L in patients weighing \u226474\u2009kg and &gt;74\u2009kg, respectively. Overall, male sex and increased kidney function necessitate higher fixed and weight\u2010based doses to achieve efficacy. Creatine phosphokinase elevation was observed in two patients (6.5%) and predicted to be lower with fixed versus weight\u2010based regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Fixed daptomycin dosing adjusted for sex and kidney function is expected to improve the efficacy\u2010to\u2010toxicity ratio, transitions of care, and costs compared to weight\u2010based doses. However, no empiric dosing approach is predicted to achieve \u226590% efficacy while minimizing the risk of toxicity, so therapeutic drug monitoring should be considered on a patient\u2010specific basis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.4602","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:26:39Z","timestamp":1722331599000},"page":"615-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Fixed dose daptomycin: An opportunity for pharmacokinetic\/pharmacodynamic optimization in <i>Staphylococcus aureus<\/i> infections"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-9070","authenticated-orcid":false,"given":"Katie B.","family":"Olney","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"},{"name":"Department of Pharmacy Practice and Science The University of Kentucky College of Pharmacy  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-5034","authenticated-orcid":false,"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7716-923X","authenticated-orcid":false,"given":"Jenni K.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna R.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"},{"name":"Department of Pharmacy Practice and Science The University of Kentucky College of Pharmacy  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1568-8699","authenticated-orcid":false,"given":"William J.","family":"Olney","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"},{"name":"Department of Pharmacy Practice and Science The University of Kentucky College of Pharmacy  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-8721","authenticated-orcid":false,"given":"Rebecca A.","family":"Bruning","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamron A.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle V.","family":"Casaus","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Kentucky HealthCare  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Crance","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases University of Kentucky HealthCare  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Z.","family":"Porterfield","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases University of Kentucky HealthCare  Lexington Kentucky USA"},{"name":"University of KwaZulu\u2010Natal School of Clinical Medicine  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0367-7135","authenticated-orcid":false,"given":"David S.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science The University of Kentucky College of Pharmacy  Lexington Kentucky 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