- On 4 Jun 2004 at 13:50:14, =?ISO-8859-1?Q?W=E5hlstr=F6m_Henrik?= (Henrik.Wahlstrom.-a-.mpa.se) sent the message
Hello!

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I have a question concerning Tmax. Is there a diffrence in Tmax

obtained from a single-dose study compared to a study performed at

steady state? I'm just interested in the most simple case without any

time- or dose dependency.

Kind Regards

Henrik Wahlstrom - On 4 Jun 2004 at 22:11:57, Wojciech Jawien (mfjawien.-a-.cyf-kr.edu.pl) sent the message
Dear Henrik,

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"I have a question concerning Tmax. Is there a diffrence in Tmax

obtained from a single-dose study compared to a study performed at

steady state? I'm just interested in the most simple case without any

time- or dose dependency."

Yes, there is a difference, because with each consecutive (regular)

dose the observed maximum is shifted a bit to the left (assuming the

next dose is given after the maximum is reached), relative to the time

of the dose. Here is a numerical example:

Assume C(t)=B*exp(-beta*t)-A*exp(-alpha*t), and put A=B=1.0, alpha=1.0,

beta=0.2, tau=10 (dosing interval), n = number of dose, tn = tau*(n-1)

- time of the nth dose.

Then

n tmax-tn

1 2.012

2 1.853

3 1.833

4 1.831

5 1.830

6 1.830

.....

steady state 1.830

This case the difference is about 10% of tmax single dose.

Best Regards

Wojciech Jawien

Jagiellonian Univ.

Faculty of Pharmacy

ul. Medyczna 9

30-688 Krakow, Poland.

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