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Dear David,
I would appreciate if you can post the following question to the PK/PD
discussion group.
We are doing a PK study on subcutaneous injection of human parathyroid
hormone 1-84 in hairless rats. The blood samples were taken by jugular
vein
cannulation at 0, 15', 30', 60' and every hour afterwards. The dose
are 1
microgram per kg and 10 microgram per Kg. We weren't able to detect any
hPTH 1-84 in both cases by ELISA, which is hPTH1-84 specific. The
detection
limit is 10 pg/ml. Could any one shed some light on this matter?
Thank you
for your input.
Shu-Lun (Cynthia) Chang, Ph.D.
Senior Research Scientist
Altea Therapeutics
2056 Weems Road
Atlanta, GA 30084-5207
Phone: (770) 270-0398, x-114
Fax: (770) 270-0399
e-mail: schang.-a-.alteatherapeutics.com
web: http://www.alteatherapeutics.com
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The following message was posted to: PharmPK
Metabolism is faster than absorption from the s.c. site. What does the
pk profile look like after i.v.?
Mark
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The following message was posted to: PharmPK
We don't have i.v. data yet. We also suspect that plasma sample
handling
and stability are the issue. But we are not able to pinpoint what it
is.
We let the blood sample containing EDTA sit on the ice until centrifuge.
The centrifuge is not equipped with refrigeration system. The plasma
samples are frozen immediately until analysis. We have seen the s.c. pk
profile (peaked in 5 minutes and declined to baseline in one hour) of
Sprague Dawley rats. Do you think the metabolism is faster in hairless
rats
than in Sprague Dawley rats? Thanks.
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Subcutaneous dosing leads to the formation of a reservoir with a slow
delivery rate depending on the drug's physicochemical properties. The
explanation could be that your PTH is very slowly released from the
subcutaneous compartment into the blood and then plasma concentrations
always remain BLQ.
Did you check that this was detectable when administered IV for
instance ?
Hope this helps,
Frederic
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The following message was posted to: PharmPK
Dear Shu-Lun Chang,
I have done some PTH studies in Rats following IV and SC dosing. We
found
PTH had the following PK: Vc ~ 50 mL/kg (Vss = 118 mL/kg), CL ~ 363
mL/hr/kg, at a dose of 112ug/kg.
F ~ 40%, Cmax = 105 ng/mL (28 nM) at ~ 1 hr.
Thus for a dose of 10 ug/kg you would expect peak concentrations to be
10
ng/mL much higher (1000-fold) than your LOQ of 10pg/mL.
However, while performing these studies we found PTH to be a rather
"sticky
protein" and had difficulty in recovering PTH from the dose solutions
if the
concentration was below 100 ug/mL (~70% recovery), based upon ELISA
assay.
To overcome this you can add albumin to the formulation and prevent the
loss
of the protein sticking to the glass. We tried a variety of vials;
plastic,
polypropylene etc but albumin was by far the best approach. To get
down to
low doses we used 25 uL syringes.
Hope this helps,
Steven W Martin, PhD
Amgen Inc., 30E-O-B
One Amgen Center Drive
Pharmacokinetics and Drug Metabolism Group
Thousand Oaks, CA 91320-1789
Phone (805)-447-4541
Fax (805)-375-6416
Email: swmartin.aaa.amgen.com
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The following message was posted to: PharmPK
Hello there,
Did you check for precipitation at the injection site?
Richard Molitor, R.Ph.
http://www.angelfire.com/wa/pharmacist
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)