The pharmacokinetic profile of plasma-derived mannan-binding lectin in healthy adult volunteers and patients with Staphylococcus aureus septicaemia

Peter Bang, Inga Laursen, Klaus Thornberg, Jens Schierbeck, Bjarne Nielsen, Helgi Valdimarsson, Claus Koch, Michael Christiansen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Mannan-binding lectin (MBL) is a member of the innate immune system, and MBL-deficiency affects 10-15% of Caucasians. With development of a plasma-derived MBL, substitution has become a therapeutic option in diseases associated with MBL insufficiency. The pharmacokinetics of injected MBL is weakly described, particularly in patients with infectious diseases. The pharmacokinetic profile of MBL following administration of 0.08 mg/kg to 20 healthy MBL-deficient volunteers and 0.2 mg/kg to 2 patients with Staphylococcus aureus septicaemia was established. In the volunteers, the maximal concentration was 2849 microg/l; the mean half-life (T(1/2)) was 69.6 h (14.6-114.9 h). The normalized clearance was 9x10(-6) l/minxkg, and the mean residence time was 82 h. In the patients the serum-MBL versus time curves were similar to those in the volunteers, and T(1/2) values were 36 and 40 h. In conclusion, MBL is distributed into a median volume of 3.4 l similar to the plasma volume, and the elimination in septicaemic patients was within the range of the controls. Due to the large individual variation in T(1/2), we recommend that MBL therapy, with respect to dose and infusion intervals, is based on the chosen therapeutic target (> or =1000 microg/l) and MBL serum determinations following the first infusion.
Original languageEnglish
JournalScandinavian Journal of Infectious Diseases
Volume40
Issue number1
Pages (from-to)44-8
Number of pages5
ISSN0036-5548
DOIs
Publication statusPublished - 1. Jan 2008

Keywords

  • Adolescent
  • Adult
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunologic Factors
  • Infusions, Intravenous
  • Male
  • Mannose-Binding Lectin
  • Middle Aged
  • Sepsis
  • Staphylococcal Infections

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