## steady state in WinNonlin (example) [Software]

Dear PKPDPKPD!

» Is it possible to use WinNonLin to assess the achievement of steady state on the basis of pre-dose concentrations?

Yes.

Using the example of this post we have:

In WinNonlin (v5.2) open a new workbook and enter these values.

Use only the last three values:

Data > Exclude > Selection

Tools > PK/PD/NCA Wizard (or

Select 'Linear' > Next > Model 502 (Linear) > Next > Finish

Click on the 'Data Variables' icon

Drag the time variable to the 'X variable' field, drag the concentration variable to the 'Y variable' field > OK

Model > Start Modeling (or click the 'calculator' icon)

A new linear workbook opens, navigate to the 'Non-Transposed Final Parameters' tab.

There are two parameters, namely 'INT' and 'SLOPE'.

'INT' is the estimated Cmin, but we are interested in 'SLOPE', which should be zero in 'true' steady-state.

Now look at the 'Estimate'-column, which gives a value of 0.018542 for slope.

A common method for the assessment of SS-conditions is either doing a

WinNonlin gives you the confidence interval in the columns 'PlanarCI_Lower' and 'PlanarCI_Uper' with -0.279250 and 0.316334. Since zero is included in the CI, steady state conditions are reached.

I added a little noise to the data:

Now we get a slope of 0.016875 (95% CI -1.981561 to 2.015311); still in steady state.

I'm not sure when Pharsight introduced linear models in WinNonlin (maybe in v5.0), in older versions you may use the 'LinMix Wizard' (which is a little bit confusing for a beginner), or use this ASCII-model - which is pretty simple:

» Is it possible to use WinNonLin to assess the achievement of steady state on the basis of pre-dose concentrations?

Yes.

Using the example of this post we have:

`+-----+-------+`

| t | c |

+-----+-------+

| 24 | 21.05 |

| 48 | 25.04 |

| 72 | 25.08 |

| 96 | 25.94 |

| 120 | 25.97 |

+-----+-------+

In WinNonlin (v5.2) open a new workbook and enter these values.

Use only the last three values:

Data > Exclude > Selection

Tools > PK/PD/NCA Wizard (or

`StrgF9`

)Select 'Linear' > Next > Model 502 (Linear) > Next > Finish

Click on the 'Data Variables' icon

Drag the time variable to the 'X variable' field, drag the concentration variable to the 'Y variable' field > OK

Model > Start Modeling (or click the 'calculator' icon)

A new linear workbook opens, navigate to the 'Non-Transposed Final Parameters' tab.

There are two parameters, namely 'INT' and 'SLOPE'.

'INT' is the estimated Cmin, but we are interested in 'SLOPE', which should be zero in 'true' steady-state.

Now look at the 'Estimate'-column, which gives a value of 0.018542 for slope.

A common method for the assessment of SS-conditions is either doing a

*t*-test (0.05,2-sided), or looking at the 95% confidence interval,* which should include zero.WinNonlin gives you the confidence interval in the columns 'PlanarCI_Lower' and 'PlanarCI_Uper' with -0.279250 and 0.316334. Since zero is included in the CI, steady state conditions are reached.

I added a little noise to the data:

`+-----+-------+`

| t | c |

+-----+-------+

| 24 | 18.71 |

| 48 | 22.44 |

| 72 | 22.44 |

| 96 | 25.63 |

| 120 | 23.25 |

+-----+-------+

Now we get a slope of 0.016875 (95% CI -1.981561 to 2.015311); still in steady state.

I'm not sure when Pharsight introduced linear models in WinNonlin (maybe in v5.0), in older versions you may use the 'LinMix Wizard' (which is a little bit confusing for a beginner), or use this ASCII-model - which is pretty simple:

`MODEL `

COMMANDS

NFUNCTIONS 1

NPARAMETERS 2

PNAMES 'inter', 'slope'

END

FUNCTION 1

F = inter + slope * X

END

EOM

- Weimann HJ.
*Drug concentrations and directly derived parameters.*In: Cawello W, editor.*Parameters for Compartment-Free Pharmacokinetics.*Aachen: Shaker-Verlag; 2003. p. 23-38.

—

Cheers,

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. ☼

Science Quotes

Cheers,

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. ☼

Science Quotes

### Complete thread:

- assessment of steady state in WinNonLin - pkpdpkpd, 2007-04-04 22:52
- steady state in WinNonlin (example) - Helmut, 2007-04-05 02:30
- steady state in WinNonlin (example) - pkpdpkpd, 2007-04-05 16:33
- steady state in WinNonlin (example) - Helmut, 2007-04-05 17:16
- steady state in WinNonlin (example) - pkpdpkpd, 2007-04-05 17:39
- steady state in WinNonlin… - Helmut, 2007-04-05 18:40
- steady state in WinNonlin… - pkpdpkpd, 2007-04-05 21:37
- Paired Design in WinNonlin - Helmut, 2007-04-06 00:23

- steady state in WinNonlin… - Helmut, 2007-04-05 18:40

- steady state in WinNonlin (example) - pkpdpkpd, 2007-04-05 17:39

- steady state in WinNonlin (example) - Helmut, 2007-04-05 17:16
- steady state in WinNonlin (example) - apapanas, 2018-01-03 14:44
- steady state in WinNonlin (example) - Helmut, 2018-01-04 17:11
- qt in WinNonlin - mittyri, 2018-01-04 23:13
- ‘Deep’ bug - Helmut, 2018-01-05 00:37
- Workarounds for v6.3+ - Helmut, 2018-01-08 00:40
- Workarounds for v6.3+ - apapanas, 2018-01-10 12:47

- qt in WinNonlin - mittyri, 2018-01-04 23:13

- steady state in WinNonlin (example) - Helmut, 2018-01-04 17:11

- steady state in WinNonlin (example) - pkpdpkpd, 2007-04-05 16:33

- steady state in WinNonlin (example) - Helmut, 2007-04-05 02:30