javier ☆ Spain, 2017-03-16 18:49 (2929 d 09:31 ago) Posting: # 17158 Views: 6,352 |
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Dear All Reading about nivolumab, in the EPAR, there is a confusing information regarding the half life, im wondering if you dont mind to use your expertise to answer this question, in the single dose pk study (with full pk sampling ) the half life was reported in 17 days, while in the multiple dose study (with sparse sampling) the half life was reported in 26 days, How could it be possible? How would you calculate the steady state in this situation? I quote the exact word of the EPAR "the mean terminal elimination half-life of nivolumab ranged between 17 and 27.5 days following single dose (study MDX1106-01) and Q2W administration (MDX1106-03) across the range of 0.1 to 10 mg/kg dose." Thanks in advance for your time and dedication answering it Best Regards Javier Edit: EPAR linked and category changed; see also this post #1. [Helmut] |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-03-17 14:09 (2928 d 14:11 ago) @ javier Posting: # 17160 Views: 4,980 |
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Hi javier, ❝ in the single dose pk study (with full pk sampling ) the half life was reported in 17 days, while in the multiple dose study (with sparse sampling) the half life was reported in 26 days, How could it be possible? First of all I don’t think that half lives are normal distributed. Hence, I don’t like the reported arithmetic means. ![]() ❝ How would you calculate the steady state in this situation? What do you mean by that? — 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 |
nobody nothing 2017-03-17 17:35 (2928 d 10:45 ago) @ Helmut Posting: # 17163 Views: 4,930 |
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btw nice example why I don't like discussions based on t1/2. If you ever determined it yourself you know what kind of mess this parameter is, not to speak of the pain trying to compare results from different trials (SD/MD, sampling times/duration, non-comp./comp. models, etc. pp...). — Kindest regards, nobody |
javier ☆ Spain, 2017-03-20 13:56 (2925 d 14:24 ago) @ Helmut Posting: # 17168 Views: 4,818 |
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Hi Helmut ❝ ❝ How would you calculate the steady state in this situation? ❝ ❝ What do you mean by that? first, thank you for your swift and ilustrated response, regarding the steady state question, I was wondering about how to calculate the steady state of a drug when you have two different values of half life (If I understand correctly the steady state of a drug takes 3-5 half lives) thanks again and best regards |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2017-03-20 15:40 (2925 d 12:40 ago) @ javier Posting: # 17170 Views: 4,942 |
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¡Hola Javier! ❝ I was wondering about how to calculate the steady state of a drug when you have two different values of half life See this post (especially the last sentence) and the warfarin example (slides 21–22). ![]() If you extrapolate from SD to MD you have to rely on assumptions (linear PK, no saturation/induction/inhibition/capacity-limited excretion). ❝ (If I understand correctly the steady state of a drug takes 3-5 half lives) It depends on how one defines sufficiently ‘close’ to true steady state (at t = ∞!). For a one-compartment model, IV administration
Coming back to your OP: I would trust the results of the MD study’s PopPK-model more than the SD study’s results derived by NCA. — 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 |