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The following message was posted to: PharmPK
I have single-dose time-concentration curves from dosing clindamycin
orally in pigeons. There was EXTREMELY rapid absorption with all but
one
bird having Tmax occur at the first measured concentration of 15
minutes.
I analyzed this with WinNonLin, allowing it to set the bounds during the
fit. In doing so, it assigns very large (rapid) Ka values ranging from
5
- 48 /hr (mean 30.5 / hr). My experience has been in such datasets that
one can often lower the upper bound of Ka quite a bit without affecting
lambda-z or Vd/F (one-compartment noniv model). I have however not seen
any mention in the literature on how others approach this problem.
Is it common to progressively restrict the upper bound of ka until it
begins to affect the other parameters (and then back up) or rather
should
I just report the large values as initially created by WinNonLin?
Thanks,
Cory
Cory Langston, DVM, PhD, DACVCP
College of Veterinary Medicine
Box 6100 (Spring Street for courier)
Miss. State, MS 39762-6100
phone 662-325-1265
fax 662-325-4011
email langston.at.cvm.msstate.edu
[Do you have enough data to support a two compartment model? I wonder
if this would give more reasonable ka estimates - db]
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The following message was posted to: PharmPK
Dear Cory,
You wrote: "There was EXTREMELY rapid absorption with all but
one bird having Tmax occur at the first measured concentration of 15
minutes."
You could try to apply an iv model if you do not have enough datapoints
to support modeling of the ascending part of your curve. You might
want to compare the models with and without ka to judge whether the
data justify the estimation of ka or not.
Best regards,
Jeroen
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