{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:01:51Z","timestamp":1773982911237,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The efficacy of an anti-infective drug is influenced by its protein binding (PB), since only the free fraction is active. We hypothesized that PB may vary in vitro and in vivo, and used clindamycin, a drug with high and concentration-dependent PB to investigate this hypothesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six healthy volunteers received a single intravenous infusion of clindamycin 900\u2009mg. Antibiotic plasma concentrations were obtained by blood sampling and unbound drug concentrations were determined by means of in vivo intravascular microdialysis (MD) or in vitro ultrafiltration (UF) for up to 8\u2009h post dosing. Clindamycin was assayed in plasma and MD fluid using a validated HPLC-UV (ultraviolet) method. Non-linear mixed effects modelling in NONMEM\u00ae was used to quantify the PB in vivo and in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>C max was 14.95, 3.39 and 2.32\u2009mg\/L and AUC0\u20138h was 41.78, 5.80 and 6.14\u2009mg\u00b7h\/L for plasma, ultrafiltrate and microdialysate, respectively. Calculated ratio of AUCunbound\/AUCtotal showed values of 13.9%\u00b11.8% and 14.7%\u00b13.1% for UF and microdialysate, respectively. Modelling confirmed non-linear, saturable PB for clindamycin with slightly different median (95% CI) dissociation constants (Kd) for the alpha-1 acid glycoprotein (AAG)\u2013clindamycin complex of 1.16\u2009mg\/L (0.91\u20131.37) in vitro versus 0.85\u2009mg\/L (0.58\u20131.01) in vivo. Moreover, the estimated number of binding sites per AAG molecule was 2.07 (1.79\u20132.25) in vitro versus 1.66 in vivo (1.41\u20131.79).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Concentration-dependent PB was observed for both investigated methods with slightly lower levels of unbound drug fractions in vitro as compared with in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkab140","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T21:14:16Z","timestamp":1618607656000},"page":"2106-2113","source":"Crossref","is-referenced-by-count":11,"title":["Protein binding of clindamycin<i>in vivo<\/i>by means of intravascular microdialysis in healthy volunteers"],"prefix":"10.1093","volume":"76","author":[{"given":"Beatrix","family":"Wulkersdorfer","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian G","family":"Wicha","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, 20146, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizaveta","family":"Kurdina","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan F","family":"Carrion Carrera","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8175-3028","authenticated-orcid":false,"given":"Peter","family":"Matzneller","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"},{"name":"Service of Rheumatology, Hospital of Silandro (SABES-ASDAA), Via Ospedale, 339028, Silandro-Schlanders, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-1936","authenticated-orcid":false,"given":"Valentin","family":"Al Jalali","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias G","family":"Vossen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Riesenhuber","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Lackner","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, W\u00e4hringer G\u00fcrtel 18-20, 1090, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Dorn","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, University of Regensburg, Universit\u00e4tsstra\u00dfe 31, 93053, Regensburg, 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