Does anyone know the volume of distribution and half-life of IgGBack to the Top
(endogenously produced, not exogenously administered) in rats? I am
also curious about IgG distribution to individual tissues and
interstitial fluid.
Thank you,
Stephanie Gozum
University of Minnesota Medical School
Department of Pharmacology
gozum002.-at-.umn.edu
Why would the endogenous and exogenous be different?Back to the Top
I don't know if endogenous and exogenous IgG Vd and t1/2 would beBack to the Top
different.
Specifically, my question is regarding endogenously produced drug
specific-IgG following vaccination against a specific compound (active
immunization). The contrast would be passive immunization with drug
specific-IgG produced in a different animal, isolated and exogenously
administered either iv or ip to the experimental animal (rat) . In
active immunization, drug-specific IgG would be replenished by the immune
system, whereas this is not the case following passive administration of
purified antibody. I wondered if the route of administration used in passive
immunization could have an impact on Vd and tissue distribution of IgG,
in comparison to endogenously produced IgG Vd . I have one reference
describing IgG pharmacokinetics of exogenously administered IgG
(Bazin-Redureau MI, Renard CB and Scherrmann JG (1997) Pharmacokinetics
of heterologous and homologous immunoglobulin G, F(ab')2 and Fab after
intravenous administration in the rat. Journal of Pharmacy and
Pharmacology 49:277-281) Their estimate for IgG Vd is four times the plasma volume in rat.
Stephanie Gozum
University of Minnesota Medical School
Department of Pharmacology
gozum002.at.umn.edu
Dear Stephanie:Back to the Top
Your question regarding endogenous vs. exogenous IgG disposition is
interesting. The elimination, and perhaps the distribution, of IgG is
influenced by the Brambell receptor (also known as FcRn, FcRp, and
FcRb). It
is known that the affinity of this receptor is dependent on the IgG
subclass
(see ref #1, below) and on the species of IgG (see ref #2). For
example, in
man, IgG1 shows a longer t1/2 than IgG3. Additionally, mouse IgG is
associated with a t1/2 of ~2 d in man, while human IgG is associated
with a
t1/2 of ~30 d in man. So, exogenous IgG may show different disposition
characteristics than endogenous IgG if the exogenous IgG is obtained
from a
different species and/or if the subclass distribution of the exogenous
IgG
differs from the subclass distribution of endogenous IgG.
I do not know of any very good information on the distribution and
elimination of endogenous IgG in rats. However, you may be interested in
some of the work that my group has published regarding the
pharmacokinetics
of murine monoclonal antibodies in rats (e.g., see ref 3-5).
Hope this helps!
J. Balthasar
Joseph P. Balthasar, Ph.D.
Associate Professor
Department of Pharmaceutical Sciences
University at Buffalo
The State University of New York
457B Cooke Hall
Buffalo, New York 14260
Tel: 716-645-2842, x 270
Fax: 716-645-3693
References:
1. Kim J-K, Firan M, Radu CG, Kim C-H, Ghetie V, Ward ES 1999. Mapping
the
site on human IgG for binding of the MHC class I-related receptor, FcRn.
Eur. J. Immunol 29:2819-25.
2. Ober RJ, Radu CG, Ghetie V and Ward ES 2001. Differences in
promiscuity
for antibody-FcRn interactions across species: implications for
therapeutic
antibodies. Int Immunol 13:1551-9.
3. Hansen RJ and Balthasar JP 2001. Pharmacokinetics, pharmacodynamics,
and
platelet binding of 7E3, a murine anti-glycoprotein IIb/IIIa monoclonal
antibody in the rat. Journal of Pharmacology and Experimental
Therapeutics
298:165-171.
4. Hansen RJ and Balthasar JP 2002. Effects of intravenous
immunoglobulin on
platelet count and antiplatelet antibody disposition in a rat model of
immune thrombocytopenia. Blood 100:2087-2093.
5. Hansen RJ and Balthasar JP 2003. PK/PD modeling of the effects of
intravenous immunoglobulin on the disposition of anti-platelet
antibodies in
a rat model of immune thrombocytopenia. Journal of Pharmaceutical
Sciences
92:1206-1215.
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