jag009
★★★

NJ,
2014-09-16 18:42
(3481 d 22:07 ago)

Posting: # 13525
Views: 6,303
 

 factors affecting Tmax [PK / PD]

Hi all,

Question, maybe elementary but need some hints...

What factors can lead to a long Tmax like 7-8 hours? Lets say the drug 1) is BCS Class 1, 2) dissolution is completed within 1 hour (NLT 80% in 30 mins)?

1) Site specific/region specific absorption such as drug absorption does not take place until the lower part of the small intestine?
3) Saturable carrier transport?
2) Highly protein bound properties?

Thanks
John
luvblooms
★★  

India,
2014-09-18 09:02
(3480 d 07:46 ago)

@ jag009
Posting: # 13534
Views: 5,275
 

 factors affecting Tmax

Hey John

Some questions First

❝ What factors can lead to a long Tmax like 7-8 hours? Lets say the drug 1) is BCS Class 1, 2) dissolution is completed within 1 hour (NLT 80% in 30 mins)?

❝ 1) Site specific/region specific absorption such as drug absorption does not take place until the lower part of the small intestine?


(Or the absorption happens across the GIT with higher absorption in certain sections rich)

❝ 3) Saturable carrier transport? (What if the carrier is not ditibuted through out GIT?? )


❝ 2) Highly protein bound properties?



Would like to add some more
a) Cmax build up by hepatic recirculation (typical example Ezetemibe and Raloxifene)

d) Tissue distribution (If I am right Amlodipine is the typical example of this case ;-))

I had a couple of papers related to some specific highly soluble drugs with longer Tmax. Give me a couple of days I would try to find them out.

~A happy Soul~
jag009
★★★

NJ,
2014-09-19 19:09
(3478 d 21:39 ago)

@ luvblooms
Posting: # 13544
Views: 5,213
 

 factors affecting Tmax

Thanks Bloom,

❝ Would like to add some more

❝ a) Cmax build up by hepatic recirculation (typical example Ezetemibe and Raloxifene)


❝ d) Tissue distribution (If I am right Amlodipine is the typical example of this case ;-))


❝ I had a couple of papers related to some specific highly soluble drugs with longer Tmax. Give me a couple of days I would try to find them out.


One more: drugs with long half life will show increased Tmax.

John
luvblooms
★★  

India,
2014-09-21 07:29
(3477 d 09:20 ago)

@ jag009
Posting: # 13551
Views: 5,184
 

 factors affecting Tmax

Hey John,

❝ One more: drugs with long half life will show increased Tmax.


Would differ on this one cos it is not always true.

Remember Tacrolimus Thalf ~48hrs but tmax~2 hrs
Similar story for Ibandronate, Risedronate etc where thalf >48hrs but tmax<2hrs.

~A happy Soul~
nobody
nothing

2014-09-21 18:58
(3476 d 21:50 ago)

@ luvblooms
Posting: # 13552
Views: 5,075
 

 factors affecting Tmax

❝ ❝ One more: drugs with long half life will show increased Tmax.


Actually, I don't see the mechanism for that, rapid absorption might occur, no matter what the terminal elimination looks like. If you have flip-flop kinetics, it's a different story...

Kindest regards, nobody
Croosov
☆    

Germany,
2014-09-24 20:24
(3473 d 20:24 ago)

@ luvblooms
Posting: # 13568
Views: 5,108
 

 factors affecting Tmax

If it is a study under steady state conditions a possible late tmax could be found because the subject took the drug too early, before the last pk blood sample was drawn...

Anyway, is it allowed to exclude this datapoints from analysis?
UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
119 visitors (0 registered, 119 guests [including 7 identified bots]).
Forum time: 15:49 CET (Europe/Vienna)

With four parameters I can fit an elephant,
and with five I can make him wiggle his trunk.    John von Neumann

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5