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Ken Peh ★ Malaysia, 2013-02-25 14:58 (4867 d 04:06 ago) Posting: # 10117 Views: 7,319 |
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Dear Friends, The test tablet contains Chlorzoxazone 250mg and Paracetamol 300mg. The reference tablet contains only Chlorzoxazone 200mg. What is the best way to run BE study ? Can we ignore the presence of paracetamol ? Give 4 tablets of test and 5 tablets of reference to make sure the dose is equal. Your comments are highly appreciated. Regards, Ken |
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Helmut ★★★   Vienna, Austria, 2013-02-26 17:12 (4866 d 01:52 ago) @ Ken Peh Posting: # 10125 Views: 6,219 |
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Dear Ken! ❝ The test tablet contains Chlorzoxazone 250mg and Paracetamol 300mg. The reference tablet contains only Chlorzoxazone 200mg. I don’t know the Malaysian requirements for FDCs. In many regulations you have to provide a clinical justification. As a starter I recommend EMA’s guideline. ❝ What is the best way to run BE study ? Can we ignore the presence of paracetamol ? No, you can’t. Even if you find literature data demonstrating lack of PK interaction between the two APIs you cannot exclude it for the reference formulations (excipients,…). The GL calls for demonstrating BE in a 2×2 cross-over study with “the free combination of the recognised reference formulations of the individual monocomponents and the marketing formulation (fixed combination)” – of course at the same dosages. ❝ Give 4 tablets of test and 5 tablets of reference to make sure the dose is equal. Theoretically, yes. But you would have to include 1200 mg of paracetamol in the reference arm as well – which is a quite high single dose (maximum daily dose 4000 mg). 1000 mg of chlorzoxazone is far above the maximum daily dose of 650 mg. I don’t see how one could justify such a study. — 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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Ken Peh ★ Malaysia, 2013-02-28 16:39 (4864 d 02:26 ago) @ Helmut Posting: # 10133 Views: 6,132 |
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Dear Helmut, Thank you. ❝ Theoretically, yes. But you would have to include 1200 mg of paracetamol in the reference arm as well which is a quite high single dose (maximum daily dose 4000 mg. 1000 mg of chlorzoxazone is far above the maximum daily dose of 650 mg. If we use 2 tablets of test (2x250 mg chlorzoxazone) and 2 tablets of reference (2x200mg chlorzoxazone), the dose is justifiable. Nevertheless, the dose of test and reference is different. According to BE guideline, the dose to compare must be the same, right ? Who is supposed to provide the paracetamol in the reference arm ? Buy any brand from the market ? The problem is no tablet containing 600 mg of paracetamol in the market. Possible to run BE study where test and reference product contain different dose ?? Can normalization be used. The plasma concentration of test and reference is multiplied a factor based on the amount of dose given. Thank you in advance for your kind advice. Regards, Ken |
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kumarnaidu ★ Mumbai, India, 2014-03-19 11:43 (4480 d 07:22 ago) @ Ken Peh Posting: # 12664 Views: 5,335 |
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Dear All, If we want to demonstrate BE for an FDC in which one drug is highly variable (CV>30%)and other one with CV ~20% then in this case should we opt scaled approach(replicate design) or 2x2 crosover design? — Kumar Naidu |
Ing. Helmut Schütz