PharmPK Discussion - Prediction of Steady-state parameters from single dose

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On 15 Sep 2003 at 10:24:29, Hanna-Liza Jooste (hanna-liza.jooste.-at-.qdotpharma.com) sent the message


Dear all,

I need to predict steady-state parameters from single dose results
(this is new to me).
Can anyone guide me with information on how to do this?...i.e. basic
principles to use?

Thanks
Hanna-Liza

Biostatistician
QdotPharma
South Africa

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On 16 Sep 2003 at 09:30:41, Toufigh Gordi (tgordi.-a-.buffalo.edu) sent the message


The following message was posted to: PharmPK

Dear Hanna-Liz,

Generally, it should be quite simple. You may obtain estimates of CL
and Vd from your single dose study and use them to predict Css
according to:

1) Css= Dose*F / (CL*tau) or
2) Css=R0/CL or
3) Css=AUC (single dose)/tau

where F is bioavailability, tau is dosing frequency, and R0 is infusion
rate. The volume term will help you to estimate the maximum and minimum
concentrations at steady state according to:

4) Css,max= D*F / (Vd*(1-exp(-k x tau))
5) Css,min= Css,max*exp (-k x tau)

where k is equal to CL/Vd. Knowing the half-life of the compound will
help you to have an estimation of how long it will take to reach the
Css, i.e. roughly after 4 half-lives.

There are a couple of issues one should be aware of. If your aim with
repeated dosing is to maintain a certain concentration (Css),
accumulation takes place, meaning that your Css will be higher than the
concentrations observed after the initial single dose. One must make
sure that the kinetics of the compound is the same, i.e. CL or Vd are
not changed with concentration. Thus, your single dose study should
have covered several different doses.

The second issue is the variability, including inter-occasional
variability. This could become a major issue, specially if oral doses
are given. Different variability terms can be estimated using data from
the single dose study.

Toufigh Gordi

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On 19 Sep 2003 at 10:29:17, "David S. Farrier" (DFarrier.-at-.SummitPK.com) sent the message


The following message was posted to: PharmPK

Hanna-Liza

There is a handy list of pharmacokinetic equations available on our web
site at www.SummitPK.com that includes calculations of multiple dose
parameters from single dose data.

While there, take a look at our pharmacokinetics data analysis software
PK Solutions, which makes pharmacokinetic analysis easy, and includes
extrapolation of single dose data to multiple dose results.

David

David S. Farrier
Summit Research Services
www.SummitPK.com

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