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pjs ★ India, 2015-04-23 13:55 (3650 d 20:55 ago) Posting: # 14734 Views: 9,374 |
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Hi all, Would like to know your opinion regarding the biowaiver of the Simvastatin oral suspension. Linear PK is reported in the mentioned dose range Site of action of the drug is liver and is mainly getting accumulated in the liver It is reported that, plasma concentration of the drug is correlated with the adverse event of the drug but not with the efficacy In reported literature, 30 % increase in AUC did not cause change in the efficacy Excipients in the formulation are unlikely to affect the GI absorption Drug is not getting accumulated in the body Absorption is constant over the dose range of 20-80 mg for small particles (20 µm) BCS class II If the 90 % or more particles in the formulation have particle size less than 20 µm and test drug shows similar invitro disso with the ref can biowaiver be applied in this particular case? Regards, PJS Edit: Category changed. [Helmut] |
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pjs ★ India, 2015-05-15 16:55 (3628 d 17:54 ago) @ pjs Posting: # 14832 Views: 6,969 |
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Dear all, can u please share your views for the mentioned? Regards, PJS |
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Dr_Dan ★★ Germany, 2015-05-18 11:58 (3625 d 22:51 ago) @ pjs Posting: # 14847 Views: 6,963 |
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Dear PJS Applying for a BCS-based biowaiver is restricted to highly soluble drug substances with known human absorption (BCS class I&III). As you already stated above simvastatin is no highly soluble drug (BCS class II with a high intra-subject variability). Only if an active substance is considered highly soluble, it is reasonable to expect that it will not cause any bioavailability problems. In case of simvastatin you will not be able to determine the formulation effect unless you have performed a BE study. Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
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pjs ★ India, 2015-05-18 17:31 (3625 d 17:19 ago) @ Dr_Dan Posting: # 14850 Views: 7,011 |
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Dear Dr_Dan, Thanks for your response. ❝ Applying for a BCS-based biowaiver is restricted to highly soluble drug substances with known human absorption (BCS class I&III). Yes. ❝ In case of simvastatin you will not be able to determine the formulation effect unless you have performed a BE study. Main aim of the BE study is to compare the rate and extent of absorption. However in this particular test, drug efficacy is not correlated with plasma concentration as evident from no change in efficacy upon increase in plasma concentration in one reported drug intercation study. Also drug is not getting accumulated in the body so no risk of drug build up upon chronic dosing and no safety issue. Absorption is constatnt over the dose range for smaller particles and also the excipients in the formulation are similar/do not affect GI motility and hence no difference than innovator in rate of absorption can be sought. Please suggest. Regards, PJS |
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nobody nothing 2015-05-18 18:23 (3625 d 16:27 ago) @ pjs Posting: # 14851 Views: 6,866 |
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I would suggest you invest 2-3 hours to study the PK and PD of simvastatin in detail. Many things will become clearer then... — Kindest regards, nobody |
Ing. Helmut Schütz