PharmPK Discussion - High MW PEG animal and human PK

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On 1 Mar 2003 at 11:28:04, "ANDREI KONRADI" (sslawk.-a-.msn.com) sent the message


Dear PK Experts,

I am in the process of evaluating a proposal for an injectable human
therapeutic agent comprised of a very active small molecule permanently
conjugated to high molecular weight (>/= 50 KD) poly ethylene glycol
(PEG). The intent of permanent conjugation to PEGis to limit
exposureto the blood stream, and to increase half-life, so that weekly
or biweekly injectioncould be efficacious and safe. Of course,
permanent PEG conjugation mightdecrease the activity of the small
molecule towards it's target, but I anticipate this effect could be
measurable in vitro, at an early stage in the execution of the proposal.

I am appealing to you for assistance in understanding PK and ADMEfor
high molecular weight PEGs. I am a Ph.D. medicinal chemist with nine
years of industrial drug discovery experience, and I am familiar
withPK and ADME for small molecules. However, I realize PK and
ADMEforhigh molecular weight PEGs, and conjugates thereof, may be
subject to some unique effects, which are unfamiliar to me.

Can any of you direct me to experts in the field of PK and ADMEfor
high molecular weight PEGs, who may be available for consultation?

Can any of you direct me to literatureregarding the human PK and ADME
for high molecular weight PEGs?

Many Thanks,

Andrei W. Konradi, Ph.D.

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