NONMEM Users Network Archive

Hosted by Cognigen

RE: Variability on infusion duration

From: Paul Hutson <paul.hutson>
Date: Thu, 17 Dec 2020 14:55:55 +0000

Thanks to you all. I am trying several of these approaches and will report back!

Paul Hutson, PharmD, BCOP
Professor
UWisc School of Pharmacy
T: 608.263.2496
F: 608.265.5421

-----Original Message-----
From: owner-nmusers@globomaxnm.com <owner-nmusers@globomaxnm.com> On Behalf Of Bill Denney
Sent: Wednesday, August 05, 2020 12:38 PM
To: Leonid Gibiansky <lgibiansky atricia Kleiner <pklei05@uni-bonn.de>; nmusers@globomaxnm.com
Subject: RE: [NMusers] Variability on infusion duration

Similar to Leonid's solution, you can try using an exponential distribution:

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 obomaxnm.com> On Behalf Of Leonid Gibiansky
Sent: Wednesday, August 5, 2020 12:51 PM
To: Patricia Kleiner <pklei05@uni-bonn.de>; nmusers@globomaxnm.com
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 Thu Dec 17 2020 - 09:55:55 EST

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.