Log in
Register|
jag009 ★★★ NJ, 2020-02-03 21:15 (1763 d 00:07 ago) Posting: # 21132 Views: 4,904 |
|
|
Hi all, I seek your opinion on the follow: If you are being asked to design a PK study to capture single dose and SS PK profiles for a drug product, which dosing and sampling design would you use? A) On Day 1 dosing, PK sample from time 0 to X (wait a day to a few days or whatever so to capture 1/2 life). Repeat dosing for x number of days to hit steady state (while collecting predose samples to assess SS), then capture SS pk profile from 0 - x hours as per dosing interval (if dosing interval 6 hours then stop at 12 hrs). B) Capture day 1 PK from time 0 to end of dosing interval, repeat dosing for x # of days (base on dosing interval) to hit SS. On last day of dosing capture time 0 - x (x = whatever hrs needed to fully capture the elimination phase + half-life). I have seen both designs but I (and my former bosses) prefer method A. The only drawback I see from A is it takes longer time. Thx J |
|
mittyri ★★ Russia, 2020-02-03 22:05 (1762 d 23:17 ago) @ jag009 Posting: # 21136 Views: 3,995 |
|
|
Hi John, citing our Hero: If one is really interested in λz and has no SD-phase in the study, sampling should continue until concentrations from previous doses are washed out – I would expect any estimate within the MD-profile to be biased towards faster elimination. ❝ I have seen both designs but I (and my former bosses) prefer method A. The only drawback I see from A is it takes longer time. why does A take longer time? Edit: Changed to internal link; see also this post #7. [Helmut] — Kind regards, Mittyri |
|
jag009 ★★★ NJ, 2020-02-03 22:29 (1762 d 22:53 ago) @ mittyri Posting: # 21137 Views: 4,055 |
|
|
Thanks Mittyri, Can you try the above link? I tried and I got some 404 error... ❝ ❝ I have seen both designs but I (and my former bosses) prefer method A. The only drawback I see from A is it takes longer time. ❝ why does A take longer time? Sorry I made a mistake. Retracting my statement (above). john Edit: Link corrected. [Helmut] |
|
Helmut ★★★   Vienna, Austria, 2020-02-04 01:57 (1762 d 19:26 ago) @ jag009 Posting: # 21138 Views: 3,983 |
|
|
Hi John, ❝ If you are being asked to design a PK study to capture single dose and SS PK profiles for a drug product, which dosing and sampling design would you use? It depends on which question you want to answer. ❝ A) On Day 1 dosing, PK sample from time 0 to X (wait a day to a few days or whatever so to capture 1/2 life). Repeat dosing for x number of days to hit steady state (while collecting predose samples to assess SS), then capture SS pk profile from 0 - x hours as per dosing interval (if dosing interval 6 hours then stop at 12 hrs). Fine and the standard approach if
❝ B) Capture day 1 PK from time 0 to end of dosing interval, repeat dosing for x # of days (base on dosing interval) to hit SS. On last day of dosing capture time 0 - x (x = whatever hrs needed to fully capture the elimination phase + half-life). To characterize the PK of a new drug by PK modeling you would always go with this approach and sample as long as possible. Funky things may happen in nonlinear PK (auto-induction / -inhibition, capacity-limited elimination, …); see this example. — 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 |
|
mittyri ★★ Russia, 2020-02-04 10:02 (1762 d 11:20 ago) @ Helmut Posting: # 21140 Views: 4,011 |
|
|
Hi Helmut, ❝ ❝ B) Capture day 1 PK from time 0 to end of dosing interval, repeat dosing for x # of days (base on dosing interval) to hit SS. On last day of dosing capture time 0 - x (x = whatever hrs needed to fully capture the elimination phase + half-life). ❝ ❝ To characterize the PK of a new drug by PK modeling you would always go with this approach and sample as long as possible. Funky things may happen in nonlinear PK (auto-induction / -inhibition, capacity-limited elimination, …) I don't think the proposed scheme is good enough for modelling such difficult things. There are no Ctau's planned. Moreover, I would mix the A and B for that purpose. And sorry for a broken link, I cannot carve in my mind that tags for years  — Kind regards, Mittyri |
|
Helmut ★★★ Vienna, Austria, 2020-02-04 13:17 (1762 d 08:06 ago) @ mittyri Posting: # 21143 Views: 3,978 |
|
|
Hi mittyri, ❝ I don't think the proposed scheme is good enough for modelling such difficult things. There are no Ctau's planned. Correct, pre-dose values are required. I overlooked that in John’s post. ❝ Moreover, I would mix the A and B for that purpose. Stop sampling in SS at 6 (or even 24 hours)? I wouldn’t do that. You might not be able to estimate deeper compartments from SD due to analytical limitations. ❝ And sorry for a broken link, I cannot carve in my mind that tags for years No worries. — 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 |
|
mittyri ★★ Russia, 2020-02-04 13:38 (1762 d 07:44 ago) @ Helmut Posting: # 21144 Views: 3,922 |
|
|
Hi Helmut, ❝ ❝ Moreover, I would mix the A and B for that purpose. ❝ Stop sampling in SS at 6 (or even 24 hours)? I mean to sample as long as possible in SD and SS both — Kind regards, Mittyri |
Ing. Helmut Schütz