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

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• 作者：Philip D. Worboys ; Shekman L. Wong…
• 关键词：Telavancin ; Lipoglycopeptide ; Renal impairment ; Pharmacokinetics ; Hydroxypropylbetadex
• 刊名：European Journal of Clinical Pharmacology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：71
• 期：6
• 页码：707-714
• 全文大小：462 KB
• 参考文献：1.Krause KM, Renelli M, Difuntorum S, Wu TX, Debabov DV, Benton BM (2008) In vitro activity of telavancin against resistant gram-positive bacteria. Antimicrob Agents Chemother 52(7):2647-652View Article PubMed Central PubMed
  2.Higgins DL, Chang R, Debabov DV, Leung J, Wu T, Krause KM, Sandvik E, Hubbard JM, Kaniga K, Schmidt DE Jr, Gao Q, Cass RT, Karr DE, Benton BM, Humphrey PP (2005) Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 49(3):1127-134View Article PubMed Central PubMed
  3.Lunde CS, Hartouni SR, Janc JW, Mammen M, Humphrey PP, Benton BM (2009) Telavancin disrupts the functional integrity of the bacterial membrane through targeted interaction with the cell wall precursor lipid II. Antimicrob Agents Chemother 53(8):3375-383View Article PubMed Central PubMed
  4.Health Canada (2010) VIBATIV?. Available at http://?www.?hc-sc.?gc.?ca/?dhp-mps/?alt_?formats/?pdf/?prodpharma/?sbd-smd/?phase1-decision/?drugmed/?sbd_?smd_-010_?vibativ_-07792-eng.?pdf . Accessed 19 March 2015
  5.VIBATIV? [package insert] (2009). South San Francisco, CA: Theravance, Inc. Available at: http://?www.?vibativ.?com . Accessed 19 March 2015
  6.Clinigen Healthcare Ltd (2014) VIBATIV summary of product characteristics. Available at: http://?www.?ema.?europa.?eu/?docs/?en_?GB/?document_?library/?EPAR_-_?Product_?Information/?human/-01240/?WC500115364.?pdf . Accessed 19 March 2015
  7.Shaw JP, Seroogy J, Kaniga K, Higgins DL, Kitt M, Barriere S (2005) Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects. Antimicrob Agents Chemother 49(1):195-01View Article PubMed Central PubMed
  8.Wong SL, Barriere SL, Kitt MM, Goldberg MR (2008) Multiple-dose pharmacokinetics of intravenous telavancin in healthy male and female subjects. J Antimicrob Chemother 62(4):780-83View Article PubMed
  9.Shaw JP, Cheong J, Goldberg MR, Kitt MM (2010) Mass balance and pharmacokinetics of [14C]telavancin following intravenous administration to healthy male volunteers. Antimicrob Agents Chemother 54(8):3365-371View Article PubMed Central PubMed
  10.Goldberg MR, Wong SL, Shaw JP, Kitt MM, Barriere SL (2010) Single-dose pharmacokinetics and tolerability of telavancin in elderly men and women. Pharmacotherapy 30(8):806-11View Article PubMed
  11.Wong SL, Sorgel F, Kinzig M, Goldberg MR, Kitt MM, Barriere SL (2009) Lack of pharmacokinetic drug interactions following concomitant administration of telavancin with aztreonam or piperacillin/tazobactam in healthy participants. J Clin Pharmacol 49(7):816-23View Article PubMed
  12.Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31-1View Article PubMed
  13.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130(6):461-70View Article PubMed
  14.Tukey JW (1977) Exploratory data analysis. Addison-Wesley
  15.Mohr JF, Finkel KW, Rex JH, Rodriguez JR, Leitz GJ, Ostrosky-Zeichner L (2004) Pharmacokinetics of intravenous itraconazole in stable hemodialysis patients. Antimicrob Agents Chemother 48(8):3151-153View Article PubMed Central PubMed
  
• 作者单位：Philip D. Worboys (1)
  Shekman L. Wong (2)
  Steven L. Barriere (1)
  
  1. Theravance Biopharma US, Inc., 901 Gateway Boulevard, South San Francisco, CA, 94080, USA
  2. AbbVie Biotherapeutics Corp., Redwood City, CA, 94063, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1041

文摘

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--9) or 10?mg/kg (study B, n--3). 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<sub>0–∞sub>]) 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?±-.6 in study A and 6.5?±-.9 in study B to 14.5?±-.3 and 11.8?±-.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?±-.1 in study A and 17.0?±-.2 in study B to 6.18?±-.63 and 6.5?±-.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.