Log in
RegisterPK parameters from multiple doses [PK / PD]
posted by Helmut 
– Vienna, Austria, 2017-11-19 11:24 (2343 d 05:23 ago) – Posting: # 17991
Views: 9,102
Hi Jeewaka,
Not easy. You could only perform modeling assuming (!) linear PK (clearance will not change over time). Given your sampling schedule I guess it will be very difficult to model anything beyond a simple one compartment model (e.g., ≥2, Michaelis-Menten elimination, circadian rhythms influencing the PK after the morning/evening doses, saturation of metabolising enzymes after accumulation, auto-induction or inhibition …). Even then you get only PK parameters describing the overall behaviour of the drug – not “of the single dose”. See this example of auto-induction (slides 21–22). With your sampling schedule I guess it would be impossible.* Next time I strongly suggest to sample at the pre-doses to get an idea. Much better to sample after the first dose as well.
The combination of some data and an aching desire
for an answer does not ensure that a reasonable answer
can be extracted from a given body of data. John W. Tukey
❝ […] a PK study where multiple doses are given […] to estimate the PK parameters of the single dose from the blood concentrations of multiple dosing.
❝ is this possible?
Not easy. You could only perform modeling assuming (!) linear PK (clearance will not change over time). Given your sampling schedule I guess it will be very difficult to model anything beyond a simple one compartment model (e.g., ≥2, Michaelis-Menten elimination, circadian rhythms influencing the PK after the morning/evening doses, saturation of metabolising enzymes after accumulation, auto-induction or inhibition …). Even then you get only PK parameters describing the overall behaviour of the drug – not “of the single dose”. See this example of auto-induction (slides 21–22). With your sampling schedule I guess it would be impossible.* Next time I strongly suggest to sample at the pre-doses to get an idea. Much better to sample after the first dose as well.
The combination of some data and an aching desire
for an answer does not ensure that a reasonable answer
can be extracted from a given body of data. John W. Tukey
- You can come up with a couple of models assuming something (i.e., to avoid over-parameterisation). Very difficult to decide which one describes the PK “best”.
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Single PK parameters from multiple PK parameters asjrm 2017-11-19 00:44 [PK / PD]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Single PK parameters from multiple PK parameters jag009 2017-11-19 06:32
- PK parameters from multiple dosesHelmut 2017-11-19 10:24
- PK parameters from multiple doses Yura 2017-11-21 11:48
- PK parameters from multiple doses SDavis 2017-11-24 10:59
- PK parameters from multiple doses nobody 2017-11-24 16:07
- PK parameters from multiple doses SDavis 2017-11-24 22:09
- PK parameters from multiple doses nobody 2017-11-27 14:13
- PK parameters from multiple doses SDavis 2017-11-28 11:34
- PK parameters from multiple doses nobody 2017-11-28 11:51
- PK parameters from multiple doses SDavis 2017-11-28 11:54
- PK parameters from multiple doses nobody 2017-11-28 11:51
- PK parameters from multiple doses SDavis 2017-11-28 11:34
- PK parameters from multiple doses nobody 2017-11-27 14:13
- PK parameters from multiple doses SDavis 2017-11-24 22:09
- PK parameters from multiple doses nobody 2017-11-24 16:07
- Single PK parameters from multiple PK parameters nobody 2017-11-21 14:54
Ing. Helmut Schütz