The pharmacokinetic profile of plasma-derived mannan-binding lectin in healthy adult volunteers and patients with Staphylococcus aureus septicaemia.
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.
Bang
Peter
P
Department of Vaccine Development, Statens Serum Institut, Copenhagen, Denmark.
Laursen
Inga
I
Thornberg
Klaus
K
Schierbeck
Jens
J
Nielsen
Bjarne
B
Valdimarsson
Helgi
H
Koch
Claus
C
Christiansen
Michael
M
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D037601:Mannose-Binding Lectin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy*
D007155:Immunologic Factors; D037601:Mannose-Binding Lectin