pjs ★ India, 2015-05-11 16:06 (3245 d 01:01 ago) Posting: # 14783 Views: 6,670 |
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Dear all, Please suggest if Propranolol Pharmacokinetics is linear or nonlinear in the dose range of 5-40mg. Regards, PJS |
Helmut ★★★ Vienna, Austria, 2015-05-11 16:46 (3245 d 00:21 ago) @ pjs Posting: # 14784 Views: 5,606 |
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Hi PJS! ❝ Please suggest if Propranolol Pharmacokinetics is linear or nonlinear in the dose range of 5-40mg. You do yourself no good posting trivial questions. Have you ever heard about ? click: I’m not aware of any marketed 5 mg strength. Can you enlighten me? — 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 |
pjs ★ India, 2015-05-11 17:06 (3245 d 00:01 ago) @ Helmut Posting: # 14785 Views: 5,543 |
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Hi Helmut, Thanks for the quick n brief response. ❝ I’m not aware of any marketed 5 mg strength. Can you enlighten me? Propranolol oral solution in the streangth of 5-40mg/5ml strength is available. If we develop oral solution in similar strength comaparing it with Innovator (tab). Data regrding PK linearity in the dose range for waiver of BE for additional strength is needed. Regards, PJS |
Dr_Dan ★★ Germany, 2015-05-11 19:30 (3244 d 21:37 ago) @ pjs Posting: # 14786 Views: 5,584 |
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Dear PJS Propranolol is almost completely absorbed after oral administration. However, it undergoes high first-pass metabolism by the liver and on average only about 25% of propranolol reaches the systemic circulation. Propranolol is a substrate for the intestinal efflux transporter, P-glycoprotein (P-gp). However, studies suggest that P-gp is not dose-limiting for intestinal absorption of propranolol in the usual therapeutic dose range. I hope this helps Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |
pjs ★ India, 2015-05-12 10:46 (3244 d 06:21 ago) @ Dr_Dan Posting: # 14787 Views: 5,534 |
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Dear DR Dan, Thanks for your response. Some of the published literature have suggested more than proportional increase at steady state in Plasma drug concentration in the dose range of 40-320mg once daily . However, some PAR have suggested linear pharmacokinetics in the dose range. (10-80 mg). There has been no mention regarding the linearity at the dose of 5mg. Please suggest. Regards, PJS |
Dr_Dan ★★ Germany, 2015-05-12 18:58 (3243 d 22:10 ago) @ pjs Posting: # 14794 Views: 5,476 |
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Dear PJS The absolute BA varies between 5 and 50%, due to a high pre-systemic metabolism. As a result, the BA and plasma levels show a large inter-individual variability and the question of linear PK cannot be answered directly. The presence of an absorption window cannot be ruled out from published data but the postulated mechanism of the permeability of propranolol: passive transport driven by the strong lipophilic nature of the substance, makes the existence of such an absorption window unlikely. In a provisional classification of the WHO Essential Drugs, this API was classified to be BCS Class I. So, from a scientific point of view this API is a candidate for granting a biowaiver. I hope this helps. Kind regards Dr_Dan — Kind regards and have a nice day Dr_Dan |