NONMEM Users Network Archive

Hosted by Cognigen

Re: Variability on infusion duration

From: Ayyappa Chaturvedula <ayyappach>
Date: Wed, 5 Aug 2020 14:58:25 -0500

Hi Patricia,
What is the purpose of your modeling exercise? I am not sure your scenario c=
ould be assigned to any particular distribution. If you intend to simulate p=
opulation from the model, then your assumptions would not be reasonable. If y=
ou have rich data, you may try individual modeling approach to estimate dura=
tion and fix in population model.

Regards,
Ayyappa

> On Aug 5, 2020, at 1:04 PM, Bill Denney <wdenney
te:
>
> Similar to Leonid's solution, you can try using an exponential di=
stribution:
>
> D1 = DUR*(1-EXP(-EXP(ETA(1))))
>
> The exponential within an exponential gives left skew and ensures that D1 =

> DUR.
>
> For subjects who you know had an incomplete infusion duration, I would add=

> an indicator variable (1 if incomplete, 0 if full duration) so that the
> subjects with complete duration have the known complete duration.
>
> D1 = DUR*(1 - Incomplete*EXP(-EXP(ETA(1))))
>
> Thanks,
>
> Bill
>
> -----Original Message-----
> From: owner-nmusers
f
> Of Leonid Gibiansky
> Sent: Wednesday, August 5, 2020 12:51 PM
> To: Patricia Kleiner <pklei05
> Subject: Re: [NMusers] Variability on infusion duration
>
> may be
> D1=DUR*EXP(ETA(1))
> IF(D1.GT.DocumentedInfusionDuration) D1=DocumentedInfusionDuration
>
>>>> On 8/5/2020 12:18 PM, Patricia Kleiner wrote:
>> Dear all,
>> I am developing a PK model for a drug administered as a long-term
>> infusion of 48 hours using an elastomeric pump. End of infusion was
>> documented, but sometimes the elastomeric pump was already empty at
>> this time. Therefore variability of the concentration measurements
>> observed at this time is quite high.
>> To address this issue, I try to include variability on infusion
>> duration assigning the RATE data item in my dataset to -2 and model
>> duration in the PK routine. Since the "true" infusion duration can
>> only be shorter than the documented one, implementing IIV with a
>> log-normal distribution
>> (D1=DUR*EXP(ETA(1)) cannot describe the situation.
>> I tried the following expression, where DUR ist the documented
>> infusion
>> duration:
>> D1=DUR-THETA(1)*EXP(ETA(1))
>> It works but does not really describe the situation either, since I
>> expect the deviations from my infusion duration to be left skewed. I
>> was wondering if there are any other possibilities to incorporate
>> variability in a more suitable way? All suggestions will be highly
>> appreciated!
>> Thank you very much in advance!
>> Patricia
Received on Wed Aug 05 2020 - 15:58:25 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.