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murthynaidu ☆ India, 2014-06-20 16:46 (3970 d 15:30 ago) Posting: # 13103 Views: 6,707 |
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Dear All, I have calculated Cτ,ss for a steady state study using the formula Clast*exp(-Kel(τ-tlast)) for the concentration data on day6. The dosing interval for the study was 12 hrs and the sampling schedule on day6 is also having 12.00 hr and extended upto 36.00 hrs. I have refered the forum and the lectures given on these topics but i am not able to get conclusion on which data i have to perform BE for Cτ,ss
MurthyNaidu Edit: Category changed. [Helmut] |
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Helmut ★★★   Vienna, Austria, 2014-06-20 17:20 (3970 d 14:56 ago) @ murthynaidu Posting: # 13104 Views: 5,638 |
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Hi Murthy, ❝ I have calculated Cτ,ss for a steady state study using the formula ❝ Clast*exp(-Kel(τ-tlast)) for the concentration data on day6. That’s only necessary if you have deviations from the planned sampling time point. Otherwise Ĉlast = Clast since
❝ The dosing interval for the study was 12 hrs and the sampling schedule on day6 is also having 12.00 hr and extended upto 36.00 hrs. Hhm, generally one would not sample in steady state beyond the dosing interval. If the drug does not show diurnal variations in PK, the target metric for extent of BA would be AUC0–τ (and no need to sample a second profile on day 6). If the drug has time-dependent PK, the target metric would by AUC0–24 (i.e., covering two profiles). Generally after the first period one would directly switch to the respective other formulation. Since you sampled at 36 hours did you employ a full washout? ❝ I have refered the forum and the lectures given on these topics but i am not able to get conclusion on which data i have to perform BE for Cτ,ss. Well, you should have stated the relevant PK metrics together with the method(s) of calculation already in the protocol, right? In analogy to AUC look at Ĉ12 or Ĉ24. — 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 |
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murthynaidu ☆ India, 2014-06-20 17:48 (3970 d 14:28 ago) @ Helmut Posting: # 13107 Views: 5,524 |
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Dear Helmut Thanks for your immediate reply. A full wash out was considered and in protocol it was stated about Cτ,ss is the concentration at the end of dosing interval in steady state. As the EMEA new guideline for MR product is suggesting for the evaluation of Cτ,ss as one of the primary parameter. I have read in the forum stating that the requirements as per the new or draft guidelines shall also be addressed to avoid further queries from regulatory at the time of submission. Since there are no time point deviations in sample collection i have to check BE for concentration at 12 hr or 24 hrs on day 6. Regards, Murthynaidu |
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Helmut ★★★ Vienna, Austria, 2014-06-20 18:17 (3970 d 13:59 ago) @ murthynaidu Posting: # 13108 Views: 5,558 |
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Hi Murthy, ❝ A full wash out was considered… Consider avoiding such a design in the future. Start administering the respective other formulation immediately after the last sample harvested in the first period. That’s called a “switch-over” design and stated in EMA’s GL: In steady-state studies, the washout period of the previous treatment can overlap with the build-up of the second treatment (direct switching), provided the build-up period is sufficiently long (at least 5 times the terminal half-life). This not only “saves” one biosample per subject, it also shortens the duration of the study and therefore reduces the chance of drop-outs.❝ …and in protocol it was stated about Cτ,ss is the concentration at the end of dosing interval in steady state. OK. ❝ […] the requirements as per the new or draft guidelines shall also be addressed to avoid further queries from regulatory at the time of submission. Correct. ❝ Since there are no time point deviations in sample collection i have to check BE for concentration at 12 hr or 24 hrs on day 6. If you have no diurnal variations / time dependent PK C12 – or C24 otherwise. Know the drug/formulation and avoid ambiguities in the next protocol.  — 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 |
Ing. Helmut Schütz