Pharmacokinetics in rabbits and anti-sphingomyelinase D neutralizing power of Fab, F(ab')(2), IgG and IgG(T) fragments from hyper immune equine plasma

Abstract

We describe the separation of whole IgG, IgG(T)-less IgG (called here merely IgG) and IgG(T) and the production of Fab and F(ab')(2) fragments. We studied the pharmacokinetics of these immunoglobulins and fragments in rabbits. Both, the isotypes and the whole IgG fragments were purified and/or produced from the same plasma lot from horses hyper immunized against sphingomyelinase D to produce anti-Loxosceles antivenom. The sphingomyelinase D neutralizing ability of the isotypes and their fragments was measured. Fab and F(ab')(2) PK was well described by a tri-exponential kinetics. IgG and IgG(T) PK, however, deviated from the tri-exponential kinetics 120h after injecting a bolus of the immunotherapeutics. The departure between tri-exponential PK and the experimental data, was shown to be due to a surge of anti-horse antibodies occurring after 120h, peaking at approximately 260h and decaying slowly afterward.