Effect of ABCC2 and ABCG2 Gene Polymorphisms and CSF‐to‐Serum Albumin Ratio on Ceftriaxone Plasma and Cerebrospinal Fluid Concentrations. (6th June 2018)

• Record Type: Journal Article
• Authors: Allegra, Sarah; Cardellino, Chiara Simona; Fatiguso, Giovanna; Cusato, Jessica; De Nicolò, Amedeo; Avataneo, Valeria; Bonora, Stefano; D'Avolio, Antonio; Di Perri, Giovanni; Calcagno, Andrea
• Is Part Of: Journal of clinical pharmacology. Volume 58:Number 12(2018)
• Page Start: 1550
• Page End: 1556
• Publication Date: 2018-06-06
• Subjects: ABCC2 -- ABCG2 -- CSF‐to‐serum albumin ratio -- CSF -- blood‐brain barrier; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.1266
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: We measured ceftriaxone pharmacokinetics in patients' plasma and cerebrospinal fluid (CSF) and assessed the influence of biometric, demographic, genetic ( ABCB1, ABCC2, ABCB11, ABCG2, and SLCO1A2 polymorphisms) and pathological features. Adult patients with signs and symptoms of central nervous system infections, receiving intravenous ceftriaxone, were enrolled. Ceftriaxone plasma and CSF concentrations were measured by high‐precision liquid chromatographic methods; allelic discrimination was performed by real‐time polymerase chain reaction. Forty‐three patients were included: median ceftriaxone maximal concentration was 15, 713 ng/mL in plasma and 3512 ng/mL in CSF with a CSF‐to‐plasma ratio of 0.3. ABCC2 1249 rs2273697 ( P = .027) and ABCG2 1194+928 rs13120400 ( P = .015) variants were significantly associated with CSF concentrations and CSF‐to‐plasma ratios. At linear regression analysis, CSF‐to‐serum albumin ratio was an independent predictor of ceftriaxone CSF concentrations ( P = .001; also in those with intact blood‐brain barrier: P = .031) and CSF‐to‐plasma ratio ( P = .001; also in those with blood‐brain barrier impairment: P = .040). We here report the role of transporters' genetic variants as well as of blood‐brain barrier permeability in predicting ceftriaxone exposure in the central nervous system.