## Steady state calculation using WinNonlin [Software]

Dear Imran!

» 1. should trough concentrations and concentration of profiling day should
» be run separately or in the same set of data to generate PK parameters?
• If you are talking about PK modeling, all values should be included in the data set. But beware: in most (all?) situations WinNonlin's stripping procedure does not provide intial estimates; they have to be provided by the user.
• If you are talking about NCA, beware of 'PK/PD/NCA Modeling Questions FAQ #2' form Pharsight's support site:
Q: When WinNonlin gives an AUC following multiple doses, is this the total AUC or the AUC for the first dose?
A: When using Noncompartmental Modeling, the AUC given in the Final Parameters table is the AUC from 0 to infinity that would occur if only the first dose had been given.
Also beware of (quoting the manual):

Time deviations in steady-state data
When using steady-state data, WinNonlin computes AUC from dose time to dose time + tau, based on the tau value set above. However, in most studies, there will be sampling time deviations. That is, if dose time = 0 and tau = 24, the last sample might be at 23.975 or 24.083 hours. In this instance, the pro­gram will estimate the AUC based on the estimated concentration at 24 hours, and not the concentration at the actual observation time. For steady state data, Cmax, Tmax, Cmin and Tmin are found using observations taken at or after the dose time, but no later than dose time+tau.

» 2. Should only trough values should be used for calculation of % fluctuation? %fluctutation (or %Peak-to-Trough Fluctuation, %PTF) is defined as:
$$\small{\%PTF=100\frac{C_{\textrm{max}}-C_{\textrm{min}}}{C_{\textrm{av}}}}$$
where $$\small{C_{\textrm{av}}=AUC_{\tau}/\tau}$$, and $$\small{C_{\textrm{max}}}$$, $$\small{C_{\textrm{min}}}$$ refer to extremes of the profile in steady state.

In WinNonlin you have to calculate %PTF manually (it's not given in the result workbook).

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