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Ciprofloxacin Tutorial - question on Dose #372

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moulirc opened this issue Aug 18, 2019 · 6 comments

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@moulirc
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commented Aug 18, 2019

cipro

I am using Ciprofloxacin data to simulate PK profile for 500 mg dose. In the Tutorial the data was extracted from Davis et al., for both IV and Oral (750 mg). Similarly, I used data from Davis et al.., for 500 mg (paper attached) to use it as a observed value.

The observed Cmax for 750 mg is around 2.74 and the predicted is around 2.69 (Example tutorial for the website). After changing the dose to 500mg reduces the Cmax to 1.97 - while the observed is around 2.64 (Data extracted from the publication - attached). Could you please let me know why there is a big change by changing the dose amount from 750 to 500mg.

Attached is the project file and the image file.

PBPK_5Q.zip

Davis_500.pdf

@StephanSchaller

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commented Aug 18, 2019

Could be due to (inter/intra-individual) variability?
The 500mg absorption looks faster to me. This might already be enough explanation for a (relatively) higher Cmax. What are the AUC values for the two observed datasets?

@moulirc

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commented Aug 19, 2019

AUC for 750 mg is 16.47 and for 500 mg is 12.98. Will there be a big differences? just by changing the amount from 750 to 500 mg? I did not change any other parameter.

PKprofile

@tobiasK2001

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commented Aug 19, 2019

Dear moulric,

you may find this paper usefull:
https://link.springer.com/content/pdf/10.1007%2Fs40262-018-0661-6.pdf

I described and updated and more universal Ciprofloxacin model compared to the version used in the WS. Further it discusses the probably a bit challenging absorption effects of the dose of Cipro and ways to overcome this.

Hope that might help you.

Best, Tobias

@JanSchlender

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commented Aug 19, 2019

Hi moulric,
The PK of Ciprofloxacin is known to be dose-linear for the therapeutic dose range. When looking at the model parametrisation, this would also be expectable with respect to the predictions. Please note, that the formulations used in the publication you refer to are different than the one used in the Davis publication for 750mg. This might explain the slightly steeper absorption for the 500mg dose.
Best,
Jan

@RobinM92

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commented Aug 19, 2019

@moulirc

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commented Aug 21, 2019

Thanks for the response. This gives me some idea what's happening.

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