Alex
☆    

Austria,
2015-08-25 19:00
(3137 d 21:39 ago)

Posting: # 15330
Views: 4,920
 

 volume of distribution at steady-state [PK / PD]

Dear all,

I am struggling with an apparently simple problem, probably someone can clear my mind.

I have PK data following IV and IP administration. Concentrations following IP administration were best described by a zero-order absoprtion model. As

AUMC/AUC = MIT ("mean input time") + MRT

and for zero-order absorption MIT = absoprtion duration divided by two (=Tabs/2)

MRTIP = AUMCIP/AUCIP - Tabs/2

Further,

CLIP = F*dose/AUCIP where F is the bioavailability.

I can estimate F by AUCIP/AUCIV (same doses were administered) and subsequently CLIP which is equal to CLIV as:

CLIP = F*dose/AUCIP = dose/AUCIV = CLIV

Does it make sense to calcualte the volume of distribution at steady-state for IP administration by MRTIP*CLIP?

Thanks for your efforts,
All the best,
Alex
d_labes
★★★

Berlin, Germany,
2015-08-26 12:47
(3137 d 03:52 ago)

@ Alex
Posting: # 15334
Views: 3,921
 

 volume of distribution at steady-state

Dear Alex,

❝ I have PK data following IV and IP administration. Concentrations following IP administration were best described by a zero-order absoprtion model. As


❝ AUMC/AUC = MIT ("mean input time") + MRT


IMHO this should read
  MRTip= AUMC/AUC = MIT + MRTiv
with AUMC and AUC from the i.p. data.
Then you get with your zero order input
  MRTiv=MRTip - MIT = MRTip - Tabs/2
This should give the same value as MRT obtained from your i.v. data, of course within some random deviations.

Together with the clearance CL (obtained from the i.v. data or as you described) you may calculate
  Vss=CL*MRTiv

Hope this helps.

Regards,

Detlew
Alex
☆    

Austria,
2015-08-26 16:05
(3137 d 00:34 ago)

@ d_labes
Posting: # 15338
Views: 3,871
 

 volume of distribution at steady-state

Dear Detlew,

thanks for your reply! Helps a lot!

All the best,
Alex
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