Pharmacokinetics and safety of recombinant anti-RhD in healthy RhD-negative male volunteers.
In this first-in-man study, we assessed the pharmacokinetics, safety and tolerability of MonoRho, a human recombinant monoclonal anti-RhD immunoglobulin G1 (IgG1) antibody. Eighteen RhD-negative healthy male volunteers were randomized in two groups to receive a single administration of 300 micro g of MonoRho either intravenously or intramuscularly. There were no symptoms of allergic or anaphylactic type reaction in any subject, and there was no evidence of any MonoRho-related changes in laboratory safety parameters. None of the subjects mounted a detectable immune response to MonoRho. Serum samples were obtained up to 91 days after injection to measure anti-D IgG concentrations by flow cytometry. After intramuscular administration of MonoRho, anti-D IgG concentrations gradually increased reaching peak levels after a mean of 3.4 days. After 3 weeks, the mean anti-D IgG concentrations after intravenous and intramuscular administration became virtually equal to each other and remained so thereafter. In both the treatment groups, the mean elimination half-life was about 18 days and thus similar to that described for plasma-derived anti-D IgG. The bioavailability of MonoRho after intramuscular administration was estimated as 46%. The excellent tolerability and safety of MonoRho as well as its expected elimination half-life supports the continued clinical development of this compound.
Bichler
J
J
ZLB Bioplasma AG, Wankdorfstrasse 10, CH-Berne 22, Switzerland. johann.bichler@zlb.com
Spycher
M O
MO
Amstutz
H-P
HP
Andresen
I
I
Gaede
K
K
Miescher
S
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D007074:Immunoglobulin G; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D010599:Pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012204:Rh-Hr Blood-Group System / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007518:Isoantibodies; D011994:Recombinant Proteins; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen