title: Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis.
abstract: The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35 g/L) receiving teicoplanin 12 mg/kg 12-hourly intravenously for 48 h followed by 12 mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15-24) g/L. After 48 h, the median (IQR) free trough (fC(min)) and total trough (tC(min)) concentrations were 2.90 (2.67-3.47) mg/L and 15.54 (10.28-19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9-47.8) L/h and 7.0 (IQR 6.8-9.8) L/h, respectively (P<0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations (P=0.174), albumin concentration did (P<0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients.
authors.affiliation: Ampath National Laboratory Services, Milpark Hospital, 9 Guild Road, Parktown, 2193 Johannesburg, South Africa. Electronic address: brinka@ampath.co.za.
authors.forename: A J
authors.initials: AJ
authors.lastname: Brink
authors.affiliation: Department of Critical Care, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: G A
authors.initials: GA
authors.lastname: Richards
authors.affiliation: Department of Orthopaedic Surgery, Milpark Hospital, 9 Guild Road, Parktown, Johannesburg, South Africa.
authors.forename: E E G
authors.initials: EE
authors.lastname: Lautenbach
authors.affiliation: Department of Medicine, Milpark Hospital, 9 Guild Road, Parktown, Johannesburg, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Rapeport
authors.affiliation: Analytical Toxicology Laboratory Services, George, South Africa.
authors.forename: V
authors.initials: V
authors.lastname: Schillack
authors.affiliation: Department of Esoteric Sciences, Ampath National Laboratory Services, National Referral Laboratory, Centurion, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: van Niekerk
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, Australia; Pharmacy Department, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000418:Albumins / Q000032:analysis*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002845:Chromatography; D002908:Chronic Disease; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000150:complications / Q000188:drug therapy*; D010361:Patients; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications / Q000188:drug therapy*; D017334:Teicoplanin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000418:Albumins; D000900:Anti-Bacterial Agents; D017334:Teicoplanin
keywords: Free; Hypoalbuminaemia; Population pharmacokinetics; Protein binding; TDM; Teicoplanin