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Registerka vs. Cmax [Dissolution / BCS / IVIVC]
posted by Helmut 
– Vienna, Austria, 2017-06-09 16:35 (2950 d 17:23 ago) – Posting: # 17477
Views: 15,347
Hi nobody,
IIRC, it was the other way ’round. Theoretically we are interested in ka, and Cmax (better together with tmax) is only a better accessible surrogate for it. In the early days of BE people tried to estimate ka indeed. For a one-compartment model Wagner-Nelson or the residual method works. But: Due to error propagation, the estimate is not very robust. For more than one compartment we have only Loo-Riegelman and deconvolution (both requiring IV data and six to ten samples up to ~2×tmax). Difficult. So, people gave up and since then Cmax is the established surrogate metric for the rate of absorption.
AFAIK, in those ol’ days BE-limits for ka were never defined. Given that Cmax is less sensitive (influenced by AUC) – even if one has data to reliably estimate ka – I guess it would be rather difficult to show BE with the common limits.
❝ Hmmm, did anybody try to establish ka as an alternative in BE?
IIRC, it was the other way ’round. Theoretically we are interested in ka, and Cmax (better together with tmax) is only a better accessible surrogate for it. In the early days of BE people tried to estimate ka indeed. For a one-compartment model Wagner-Nelson or the residual method works. But: Due to error propagation, the estimate is not very robust. For more than one compartment we have only Loo-Riegelman and deconvolution (both requiring IV data and six to ten samples up to ~2×tmax). Difficult. So, people gave up and since then Cmax is the established surrogate metric for the rate of absorption.
❝ Would be fun to see some 100s of old BE-trials re-evaluated based on ka, I guess...
AFAIK, in those ol’ days BE-limits for ka were never defined. Given that Cmax is less sensitive (influenced by AUC) – even if one has data to reliably estimate ka – I guess it would be rather difficult to show BE with the common limits.
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
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Complete thread:
- increased solubility = different PK profile? Dr_Dan 2017-06-08 16:57
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- increased solubility = different PK profile? nobody 2017-06-08 17:16
- increased solubility = different PK profile? Helmut 2017-06-08 17:18
- increased solubility = different PK profile? nobody 2017-06-08 17:22
- ka vs. CmaxHelmut 2017-06-09 14:35
- ka vs. Cmax nobody 2017-06-09 16:27
- ka vs. Cmax mittyri 2017-06-10 14:59
- ka vs. CmaxHelmut 2017-06-09 14:35
- increased solubility = different PK profile? nobody 2017-06-08 17:22
- increased solubility = different PK profile? ElMaestro 2017-06-08 17:24
- increased solubility = different PK profile? Dr_Dan 2017-06-08 17:36
- increased solubility = different PK profile? nobody 2017-06-08 17:43
- increased solubility = different PK profile? Ohlbe 2017-06-08 18:23
- increased solubility = different PK profile? nobody 2017-06-08 18:58
- increased solubility = different PK profile? ElMaestro 2017-06-08 18:45
- increased solubility = different PK profile? nobody 2017-06-08 18:57
- increased solubility = different PK profile? nobody 2017-06-09 09:38
- increased solubility = different PK profile? nobody 2017-06-08 18:57
- increased solubility = different PK profile? Dr_Dan 2017-06-08 17:36
- increased solubility = different PK profile? Kiran 2017-06-24 11:02
Ing. Helmut Schütz