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bjkim97 ☆ Korea / Seoul, 2013-06-03 13:13 (4763 d 18:00 ago) Posting: # 10712 Views: 10,385 |
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Hi Everyone. This member. I will study about the duloxetine in bioequivalence. According to the reference, ISCV in AUC and Cmax values was considerable, with the CV ranging from 46.79% to 61.89% and 35.81% to 68.18%, respectively (Clinical Therapeutics/Volume 31, Number 5, 2009) Another the reference, ISCV in AUC and Cmax values was small with the CV ranging from 13.29% and 13.16% (NDA N0. 21-427, Cymbalta) Finally the reference, ISCV in AUC and Cmax values was small the the CV ranging from 17.12% and 21.99% (Internal Data) Fast AUC(inf) AUC(t) Cmax TmaxWhy reference value this different. I reviewed this product. And this product has pushed me to the chaos. You please advise to me Best regards BJ |
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Helmut ★★★   Vienna, Austria, 2013-06-03 13:42 (4763 d 17:31 ago) @ bjkim97 Posting: # 10713 Views: 9,222 |
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Hi BJ! ❝ According to the reference, ISCV in AUC and Cmax values was considerable, with the CV ranging from 46.79% to 61.89% and 35.81% to 68.18%, respectively ❝ (Clinical Therapeutics/Volume 31, Number 5, 2009) I don’t have the reference, but in the abstract (arithmetic?) means ±SD of the doses are given. If you calculate CV=100·SD/x these values are ~CVtotal (see this post). Since generally CVinter > CVintra I would not worry. Furthermore, n=10 with three treatments have few degrees of freedom. Even if the CI is given in the paper (please check; you can calculate CVintra from it) the CV would be rather uncertain… I would trust your own data the most. If you plan another study allow for a safety margin since the PE of Cmax is not that nice. The upper confidence limit of the CV of Cmax is 26.81%. With an expected T/R-ratio of 0.86 you would need 166 (!) subjects in a 2×2 cross-over to obtain 80% power… Since you had significant differences of AUCt and Cmax (CIs did not contain 100%) consider reformulating. — 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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jag009 ★★★ NJ, 2013-06-03 19:01 (4763 d 12:12 ago) @ Helmut Posting: # 10714 Views: 9,070 |
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Are you guys referring to the following article? Clin Ther. 2009 May;31(5):1022-36. doi: 10.1016/j.clinthera.2009.05.005.If so, I don't see how you can extract the intrasubject CV since it was a one treatment (product) PK study carried out to elucidate the SD and MD PK of the drug. I agree with Helmut. Thanks John |
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Helmut ★★★ Vienna, Austria, 2013-06-03 19:19 (4763 d 11:54 ago) @ jag009 Posting: # 10715 Views: 9,037 |
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Hi John! ❝ Are you guys referring to the following article? […] ❝ If so, I don't see how you can extract the intrasubject CV since it was a one treatment (product) PK study carried out to elucidate the SD and MD PK of the drug. Maybe I’m misinterpreting the abstract (I don’t have the article): “Subjects were randomized to receive a single dose of 30, 60, or 90 mg of duloxetine.” Smelled of cross-over to me. But your interpretation (parallel) is valid as well.@BK: which design? — 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 |
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jag009 ★★★ NJ, 2013-06-03 19:51 (4763 d 11:22 ago) @ Helmut Posting: # 10716 Views: 9,097 |
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Hi Helmut, ❝ Maybe I’m misinterpreting the abstract (I don’t have the article): “Subjects were randomized to receive a single dose of 30, 60, or 90 mg of duloxetine.” Smelled of cross-over to me. But your interpretation (parallel) is valid as well.❝ @BK: which design? This gave me the idea that it was a PK evaluation study. "The 10 subjects who received the 30-mg dose in the single-dose phase continued on to the multiple-dose phase and received 30 mg of duloxetine twice daily for 7 days." I guess they randomized the subject to determine who would receive the 30/60/90 mg dose? John |
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Helmut ★★★ Vienna, Austria, 2013-06-03 20:17 (4763 d 10:56 ago) @ jag009 Posting: # 10719 Views: 9,099 |
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Hi John, ❝ "The 10 subjects who received the 30-mg dose in the single-dose phase continued on to the multiple-dose phase and received 30 mg of duloxetine twice daily for 7 days." ❝ ❝ I guess they randomized the subject to determine who would receive the 30/60/90 mg dose? My crystall ball is in the laundry, but yours seem to work well. Reasonable assumption. — 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 |
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cakhatri ★ India, 2013-06-05 20:03 (4761 d 11:10 ago) @ bjkim97 Posting: # 10731 Views: 9,052 |
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Dear BJ, I have experience with this molecule and have done at least 4-5 studies in both fast and fed conditions with Cymbalta 60mg (US & EU) as reference product. The ISCV always has been greater than 25% and less than 30%. Very simple product Regards Chirag |
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bjkim97 ☆ Korea / Seoul, 2013-06-24 04:52 (4743 d 02:21 ago) @ cakhatri Posting: # 10866 Views: 8,779 |
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Thank you for your comment. Your message has been confirmed to later. Do you give the concentration data? If possible, may i have sent to my email ![[image]](img/email.png) .Your kind help will be great strength to me. Regards BJ Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! Never post your e-mail address on a public forum (e-mail harvesters will be happily send you tons of spam). I removed it. Registered user may contact you anyway. [Helmut] |
Ing. Helmut Schütz