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msmnainar ★ India, 2012-12-20 09:36 (4938 d 21:24 ago) Posting: # 9734 Views: 3,960 |
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Hello all I need clarification regarding the measurement of metabolite for those drug having racemic activity. Both parent and its metabolites exhibit linear kinetics and its linear in pharmacokinetics, as per product label. However, both parent and its metabolites exposure are different, as per literatures. The study is for TGA submission. Thanks and regards MSMN — Sundar. M |
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drgunasakaran1 ★★  2012-12-22 13:28 (4936 d 17:32 ago) @ msmnainar Posting: # 9747 Views: 3,002 |
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Dear Mr Msmnainar, For TGA submission, estimation of parent compound alone is sufficient for those drug having racemic activity. The use of achiral bioanalytical methods is generally recommended by TGA. However, TGA recommends to measure the individual enantiomers when your drug meets all the following conditions: (1) the enantiomers exhibit different pharmacokinetics (2) the enantiomers exhibit pronounced difference in pharmacodynamics (3) the exposure (AUC) ratio of enantiomers is modified by a difference in the rate of absorption. — Dr Gunasakaran Sambandan MD Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn |
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msmnainar ★ India, 2012-12-24 07:40 (4934 d 23:20 ago) @ drgunasakaran1 Posting: # 9750 Views: 2,960 |
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Dear Dr Gunasekaran, Thanks for your reply, Guidelines stating the below points, however the drug behaviour is as mentioned below, (1) the enantiomers exhibit different pharmacokinetics - No (2) the enantiomers exhibit pronounced difference in pharmacodynamics - Not sure, no data available (3) the exposure (AUC) ratio of enantiomers is modified by a difference in the rate of absorption - Not sure, no data available Thanks, MSMN — Sundar. M |
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Helmut ★★★   Vienna, Austria, 2012-12-24 15:29 (4934 d 15:31 ago) @ msmnainar Posting: # 9754 Views: 3,033 |
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Dear MSMN! The GL continues with: The individual enantiomers should also be measured if the above conditions are fulfilled or are unknown. If one enantiomer is pharmacologically active and the other is inactive or has a low contribution to activity, it is sufficient to demonstrate bioequivalence for the active enantiomer. No idea how strict TGA enforces the “unknown” part. I changed to chiral methods almost all the time for the same reason just to learn from European regulators that most sponsors simply ignore this issue. — 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 |
Ing. Helmut Schütz