Pharmacokinetics of intravenous telavancin in healthy subjects with varying degrees of renal impairment.

Purpose: We evaluated the effect of renal impairment (RI) on the pharmacokinetics of telavancin and hydroxypropylbetadex (excipient in the telavancin drug product). Methods: Adults with normal, mild, moderate or severe RI or end-stage renal disease (ESRD) receiving haemodialysis were included in two...

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Publicado en:European Journal of Clinical Pharmacology Vol. 71; no. 6; pp. 707 - 715
Autores principales: Worboys, Philip, Wong, Shekman, Barriere, Steven
Formato: equations & formulas research tables/charts Journal Article
Publicado: Springer Nature Jun2015
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2015
      vid: 71
      iid: 6
      pid: 237
      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-015-1847-6
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        atl: Pharmacokinetics of intravenous telavancin in healthy subjects with varying degrees of renal impairment.
      aug:
        au:
          Worboys, Philip
          Wong, Shekman
          Barriere, Steven
        affil: Theravance Biopharma US, Inc., 901 Gateway Boulevard South San Francisco 94080 USA
      sug:
        subj:
          Administration, Intravenous
          Antibiotics Pharmacokinetics
          Kidney Diseases
          Dialysis Patients
          Human
          Male
          Female
          Young Adult
          Adult
          Middle Age
          Aged
          Poland
          Antibiotics Blood
          Antibiotics Urine
          Post Hoc Analysis
          Descriptive Statistics
          Adverse Drug Event
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Male
          Female
      ab: Purpose: We evaluated the effect of renal impairment (RI) on the pharmacokinetics of telavancin and hydroxypropylbetadex (excipient in the telavancin drug product). Methods: Adults with normal, mild, moderate or severe RI or end-stage renal disease (ESRD) receiving haemodialysis were included in two open-label, phase I studies of single-dose telavancin at 7.5 mg/kg (study A, n = 29) or 10 mg/kg (study B, n = 43). Pharmacokinetic analysis of telavancin and hydroxypropylbetadex plasma concentration versus time was performed in these subjects. Results: The results in studies A and B were similar: telavancin systemic exposure (area under the concentration-time curve from 0 to infinity [AUC]) increased with RI. Telavancin half-life ( h, mean ± SD) increased in subjects with severe RI compared with subjects with normal renal function from 6.9 ± 0.6 in study A and 6.5 ± 0.9 in study B to 14.5 ± 1.3 and 11.8 ± 6.7, respectively. Conversely, clearance (ml/h/kg, mean ± SD) decreased in subjects with severe RI compared with subjects with normal renal function from 13.7 ± 2.1 in study A and 17.0 ± 3.2 in study B to 6.18 ± 0.63 and 6.5 ± 1.5, respectively. Systemic exposures for hydroxypropylbetadex also increased with severity of RI. Conclusions: Results from two independent phase 1 studies suggest that dose adjustment of telavancin is required in subjects with varying degrees of RI.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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