Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients.

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  • Author(s): Belldina EB;Belldina EB; Huang MY; Schneider JA; Brundage RC; Tracy TS
  • Source:
    British journal of clinical pharmacology [Br J Clin Pharmacol] 2003 Nov; Vol. 56 (5), pp. 520-5.
  • Publication Type:
    Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print Cited Medium: Print ISSN: 0306-5251 (Print) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Wiley-Blackwell
      Original Publication: London, Macmillan Journals Ltd.
    • Subject Terms:
    • Abstract:
      Aims: Cysteamine is used to reduce tissue cystine content in patients suffering from nephropathic cystinosis. The objectives of the current study were to investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young adults with nephropathic cystinosis.
      Methods: Cysteamine bitartrate was administered to 11 cystinosis patients at their regular dose level in a single-dose, open-label, steady-state study. Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic-pharmacodynamic model.
      Results: Cysteamine was rapidly cleared from the plasma (mean CL/F = 32.3 ml min(-1) kg(-1), range = 17.3-52.2), appeared to be extensively distributed (mean Vss/F = 15.1 l, range 2.7-32.3) and exhibited a mean Tmax of 1.4 h. White blood cell cystine content post-dosing was significantly decreased compared with pre- and post-dose values (average decrement approximately 47%). A counter-clockwise hysteresis was noted in all patients, suggestive of a lag time (mean Tlag = 0.44 h, range 0.22-0.92) between drug concentration and effect.
      Conclusions: The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein.
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    • Grant Information:
      M01 RR000827 United States RR NCRR NIH HHS; M01 RR00827 United States RR NCRR NIH HHS
    • Accession Number:
      0 (Radiation-Protective Agents)
      5UX2SD1KE2 (Cysteamine)
    • Publication Date:
      Date Created: 20031204 Date Completed: 20040202 Latest Revision: 20190513
    • Publication Date:
      20231215
    • Accession Number:
      PMC1884393
    • Accession Number:
      10.1046/j.1365-2125.2003.01927.x
    • Accession Number:
      14651726