Dear NMUsers,
Some pharmacokinetic data of a monoclonal antibody (IGG1 like) administered
as 2-h infusion (single dose and repeated administration every two weeks)
show a peak concentration observed (generally 1 to 6 hours) after the end of
infusion.
At the current stage, we are aiming to develop as quickly as possible a
pragmatic PK model that can be further used to simulate alternative
administration regimens under discussion for future studies.
What could be the physiological explanation for observing a peak
concentration after the end of the infusion? Maybe can target drug-mediated
disposition, a common observation in mAbs pharmacokinetics, be - at least
part of - the answer?
Assuming a plausible explanation can be found, what would be your advice on
the more efficient modeling strategy, keeping in mind that the modeling
interest at this stage is only for simulation purpose?
Thanks in advance for any suggestion!
Fabrice
Fabrice Nollevaux,
Arlenda SA
http://www.arlenda.com www.arlenda.com
Delayd Cmax following infusion of a monoclonal antibody
Fabrice,
Standard TMDD equations that assume infusion into the central compartment will not describe this case. Two possible options (for phenomenological description) is to treat is as infusion with estimated duration (and in this case different infusion rate before and after the actual end of infusion since Tmax is significantly later than the end of infusion) or introduce the intermediate depot compartment that collects the drug during the infusion and continues to release it after the end of infusion (similar to how SC absorption is described).
Thanks
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Quoted reply history
On 10/25/2011 11:09 AM, [email protected] wrote:
> Dear NMUsers,
>
> Some pharmacokinetic data of a monoclonal antibody (IGG1 like)
> administered as 2-h infusion (single dose and repeated administration
> every two weeks) show a peak concentration observed (generally 1 to 6
> hours) after the end of infusion.
>
> At the current stage, we are aiming to develop as quickly as possible a
> pragmatic PK model that can be further used to simulate alternative
> administration regimens under discussion for future studies.
>
> What could be the physiological explanation for observing a peak
> concentration after the end of the infusion? Maybe can target
> drug-mediated disposition, a common observation in mAbs
> pharmacokinetics, be – at least part of – the answer?
>
> Assuming a plausible explanation can be found, what would be your advice
> on the more efficient modeling strategy, keeping in mind that the
> modeling interest at this stage is only for simulation purpose?
>
> Thanks in advance for any suggestion!
>
> Fabrice
>
> Fabrice Nollevaux,
>
> Arlenda SA
>
> www.arlenda.com http://www.arlenda.com