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Dear all,
In the use of PK/PD modeling different parameters can be obtained by
the models employed. When Emax modified model is employed to modeling
the data, the following sets of data were obtained:
MULTIPLE DOSE:
Drug 1
kmax= 0.869 h-1
EC50 = 9.141
Drug 2
Kmax = 0.652 h-1
EC50 = 2.119
When CONSTANT INFUSION was evaluated :
Drug 1
kmax = 0.1191 h-1
EC50 = 0.663
Drug 2
Kmax= 0.3012 h-1
EC50 = 0.305
The k obtained to control grouop was 0.06103 h-1.
Questions:
When multiple dose is used, EC50 from Drug 1 is higher than that form
Drug 2. So, Drug 2 has higher potency than drug 1. The same was
observed when constant infusion was employed. Which could be the
reasons for this observation? Drug 2 is more potent than drug 1
independently from the regime of administration?
Comparing drug 1 and 2 in multiple dosing: why drug 2 with EC50 lower
had kmax lower than drug 1? With more potency the drug had killing
rate lower. Does it make sense??
When comparing the parameters in constant infusion modifications were
obtained. EC50 from drug 2 was lower than drug 1, but now with kmax
higher than drug 1.Does it make sense?? Which could be the reason for
this observation?
Comparing drug 1 regarding diferent treatment (multiple dosing and
constant infusion) EC50 was lower in infusion than in multiple dosem
but here the kmax was lower as well.Does it make sense??
The microorganism was the same in all experiments.
THANKS IN ADVANCE FOR ANY HELP!!
Tasso.
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The following message was posted to: PharmPK
Hi
It might be that the parameter values are not very well determined -
the confidence intervals might be wide enough for there to be no
statistical difference between the two sets of estimates.
Why not simulataneouly fit the Multiple dose and infusion data to
obtain a single Kmax and EC50 for each drug? The parameters might be
better determined then.
Regards
James Yates
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Hi Yates,
the confidence intervals are not wide enough and there is statistical
difference between the two sets of estimates.
Simultaneously fit was done but the fit was inappropriate and the
parameters were out of sense. The question is still without response!
What say about the sets of estimates??
Regards,
Tasso.
[Scaling, units etc can be an issue with simultaneous fits - db]
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The following message was posted to: PharmPK
Hi
Re: Confidence intervals. Well that's cleared that up then!
The fact the fit was innapropriate when fitting both sets of data
simultaneously suggests model mispecification. The EC50 for the
multiple dosing is higher than for the constant infusion which might
mean there's tolerance forming?
Cheers
James
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The following message was posted to: PharmPK
Dear Tasso,
> The question is still without response!
> What say about the sets of estimates??
Please provide more details about your data and the models you
applied. From the information in your message no more can be said.
Your message does not make clear whether you applied different models
to the same data, or to different data sets? You mention killing of
microorganisms. In vitro or in vivo? Which models were used?
best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
Email: j.h.proost.-at-.rug.nl
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