title: Changes in the pharmacokinetics of teicoplanin in patients with hyperglycaemic hypoalbuminaemia: Impact of albumin glycosylation on the binding of teicoplanin to albumin.
abstract: There is large interindividual variability in serum teicoplanin (TEIC) concentrations after administration of a loading dose, and the factors that influence the pharmacokinetics of TEIC are disputed. The aim of this study was to clarify changes in the pharmacokinetics of TEIC that occur in patients with hyperglycaemia as well as the impact of albumin glycosylation on the pharmacokinetics of TEIC. This study consisted of retrospective and prospective investigations. The pharmacokinetic parameters of TEIC were retrospectively compared between patients receiving TEIC treatment. Ninety-four patients were divided into four groups according to their serum albumin and blood glucose concentrations [(i) hyperglycaemic hypoalbuminaemia (albumin<3.0g/dL) (n=16); (ii) non-hyperglycaemic hypoalbuminaemia (n=29); (iii) hyperglycaemic normoalbuminaemia (albumin≥3.0g/dL) (n=9); and (iv) non-hyperglycaemic normoalbuminaemia (n=40)]. In addition, the concentration of glycosylated albumin was prospectively determined in 28 patients. At 12h after administration of a loading dose, patients with hyperglycaemic hypoalbuminaemia displayed significantly lower serum TEIC concentrations (P<0.05) and higher TEIC volume of distribution (Vd) (P<0.05) than the other three groups, whereas TEIC clearance did not differ significantly among the groups. In addition, the percentage of glycosylated albumin was significantly correlated with the association constant (Ka) of TEIC for albumin (r=0.53, P=0.004) and the Vd (r=0.41, P=0.031). These results suggest that hyperglycaemic hypoalbuminaemia lowers the serum TEIC concentration, which is attributable to the decreased Ka and increased Vd of TEIC by albumin glycosylation.
authors.affiliation: Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Enokiya
authors.affiliation: Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Muraki
authors.affiliation: Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan. Electronic address: okudam@clin.medic.mie-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000737:chemistry* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D006801:Humans; D006943:Hyperglycemia; D034141:Hypoalbuminemia; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011485:Protein Binding; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry*; D017334:Teicoplanin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000418:Albumins; D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D017334:Teicoplanin
keywords: Albumin binding; Glycosylated albumin; Hyperglycaemia; Hypoalbuminaemia; Teicoplanin