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Dear All:
I have data from an in vivo study (oral administration) that is best
described by 1 comp model. I used WinNonlin model # 3 (1 comp) and model
# 5 ( 1 comp, K01 = K10). The later seems to fit the data better with
significantly lower CV% . I am just not sure when this assumption (K01 K10)
should be made. Should it be used in case of flip flop kinetics?
Any feedback about when model 5 is to be used will be greatly
appreciated.
Regards,
Andrew
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The following message was posted to: PharmPK
Dear Andrew
I am not that much sure about using model 5, criterias can be
explained by experts in a better way.
But If K01=K10, it is supossed not to be flip-flop kinetics. Because
two basic assumption for flip-flop kinetics are:
(i)The terminal portion of the conc. time curve is not parallel for
Oral and IV data, and
(ii) Ka (Absorption rate constant) is much less than Ke (Elimination
rate constant)
You can refer VLASE L et. al. "PHARMACOKINETICS OF INTRAVENOUSLY
AND ORALLY ADMINISTERED MEMANTINE IN SWINE" FARMACIA, 2011, Vol. 59
You can also refer to earlier discussion at
http://www.pharmpk.com/PK03/PK2003324.html
Kind Regards
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The following message was posted to: PharmPK
One more paper
Wijnand HP. Pharmacokinetic model equations for the one- and
two-compartment models with first-order processes in which the
absorption and exponential elimination or distribution rate constants
are equal. J Pharmcokinet Biopharmaceut. 1988;16:109-128.
Susan
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The following articles might be of interest
Bialer M. A simple method for determing whether absorption and
elimination rate constants are equal in a one-compartment open model
with first-order processes. J Pharmacokinet Biopharmaceut 1980;8:111-3.
Chan KKH and Miller KW. Nonlinear regression approach for determining
whether absorption and elimination rate constants are equal in the
one-compartment open model with first-order processes. J Pharm Sci
1983;72:574-76.
Susan
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The following message was posted to: PharmPK
The following articles might be of interest
Bialer M. A simple method for determing whether absorption and
elimination rate constants are equal in a one-compartment open model
with first-order processes. J Pharmacokinet Biopharmaceut 1980;8:111-3.
Chan KKH and Miller KW. Nonlinear regression approach for determining
whether absorption and elimination rate constants are equal in the
one-compartment open model with first-order processes. J Pharm Sci
1983;72:574-76.
Susan
[Are they ever equal except mathematically? I would be reluctant to set them equal during a modeling exercise. Your model needs to take into account the possibility that they are equal to avoid divide by zero but that can be done with an if statement or use of a differential equation model. - db]
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The following message was posted to: PharmPK
Hi Andrew, I think others on the list have given some good references -
I just wanted to add that model selection should also include using the
other diagnostic criteria that WinNonlin provides e.g. AIC, visual
inspection of fit, etc. and that it's better to assess all of the model
assessments as a whole (as well as it's intended use (Learn, Confirm,
Predict))
- rather than selecting on only one criteria. If you need to discuss
WinNonlin specific questions I welcome you to also join our discussion
forum at www.pharsight.com/extranet
Best regards,
Simon.
--
Simon.Davis.at.certara.com
Senior Scientific Consultant
Pharsight- A Certara(tm) Company
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