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Hi everyone,
Does anyone of you know the reason why the volume of distribution for
a monoclonal antibody (humanized version) could be smaller than
plasma volumen?. We got values as small as 0.02 L/Kg in human (i.e.,
cancer patients) after using a non-commercial ELISA method of
quantification. I would welcome any advice the forum can give me.
Please, references (if any) will be highly appreciate.
Cheers,
Jorge
Jorge Duconge, PhD
Associate Professor of Pharmacokinetics
Medical Sciences Campus. UPR
Dept Pharmaceutical Sciences, Suite 413C
School of Pharmacy. PO BOX 365067
San Juan PR 00936-5067
(787) 758 2525 ext. 5410
jduconge.at.rcm.upr.edu
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Jorge,
A good reference is the review from Balthasar (J Pharm Sci. 2004 Nov;
93(11):2645-68).
A volume smaller than serum volume is difficult to explain. Could the
ELISA assay be artificially high? You need to be careful if the
volume calculation is based the estimation of terminal slope (when
the terminal portion is big enough to affect the reliability of
estimating volume; unless you have collected time points to the very
end, which is not common for an antibody PK study). Use C0/Cmax for
estimating volume as an alternative (but it assumes on targeted
binding on certain organs, which cannot be excluded as many delayed
C0 upon IV dose have been observed).
Huadong Tang
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