Bioequivalence and Bioavailability Forum

Ken Peh ★ Malaysia, 2013-08-01 21:21 (4710 d 00:43 ago) Posting: # 11150 Views: 8,566	CI for Narrow Therapeutic Index Drugs [Regulatives / Guidelines] Post reply
	Dear All, Where can we find the CI for Narrow Therapeutic Index Drugs ? The same range of 0.80-1.25 applied ? Your input is highly appreciated. Thank you. Regards, Ken

jag009 ★★★ NJ, 2013-08-01 22:06 (4709 d 23:58 ago) @ Ken Peh Posting: # 11152 Views: 7,620	CI for Narrow Therapeutic Index Drugs Post reply
	Hi, ❝ Where can we find the CI for Narrow Therapeutic Index Drugs ? The same range of 0.80-1.25 applied ? FDA?

Helmut
★★★

Vienna, Austria,
2013-08-02 04:59
(4709 d 17:05 ago)

@ Ken Peh
Posting: # 11156
Views: 7,969

Lists of NTIDs

Hi Ken,

❝ Where can we find the CI for Narrow Therapeutic Index Drugs ?

In your study report. :-D

I guess you meant their acceptance ranges.

Some countries have lists (Denmark, Canada), API-specific guidances (FDA), or a Q&A document (EMA).

Denmark-DHMA
90% CI within 90.00–111.11% for AUC and C_max:
aminophylline/theophylline, lithium, vitamin K antagonists, antiepileptics apart from levetiracetam and benzodiazepines, antiarrhythmics, centrally acting anorectics, tricyclic antidepressants.
Canada-HPFP/TGD
90% CI of AUC within 90.0–112.0%, 90% CI of C_max within 80.0–125.0%:
cyclosporine, digoxin, flecainide, lithium, phenytoin, sirolimus, tacrolimus, theophylline, warfarin.
US-FDA
Narrower AR based on reference scaling (only fully replicate studies): warfarin, tacrolimus.
EU-EMA
tacrolimus 90.00–111.11% for AUC and 80.00–125.00 for C_max,
ciclosporine 90.00–111.11% for AUC and C_max.

These lists may change any time; if in doubt contact the respective authority.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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kumarnaidu ★ Mumbai, India, 2013-09-24 13:56 (4656 d 08:08 ago) @ Helmut Posting: # 11547 Views: 7,262	Lists of NTIDs Post reply
	Hi all, Can anybody tell if I am doing study for canada and the drug is NTI and the acceptance limit is 80-125 for cmax and 90-112 for AUC then what upper/lower equivalence bound I have to consider for sample size calculation. — Kumar Naidu

Helmut
★★★

Vienna, Austria,
2013-09-24 15:26
(4656 d 06:38 ago)

@ kumarnaidu
Posting: # 11550
Views: 7,426

Hi Kumar,

❝ […] what upper/lower equivalence bound I have to consider for sample size calculation.

Exactly the ones you mentioned. In most softwares you have to use the ratio, not percent.

PS: Sample size estimation – not calculation.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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Dr_Dan ★★ Germany, 2013-09-24 16:30 (4656 d 05:34 ago) @ kumarnaidu Posting: # 11552 Views: 7,212	Lists of NTIDs Post reply
	Hi it depends on the variability of either Cmax or AUC, whichever leads to the higher sample size. Kind regards Dan — Kind regards and have a nice day Dr_Dan

kvgreddy06 ☆ India, 2013-10-17 14:29 (4633 d 07:35 ago) @ Dr_Dan Posting: # 11672 Views: 7,020	Lists of NTIDs Post reply
	Hi, can i know the CI limit for Digoxin as FDA guidelines. 'Digoxin- NTI' 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! [Dr_Dan]

Dr_Dan ★★ Germany, 2013-10-17 16:29 (4633 d 05:35 ago) @ kvgreddy06 Posting: # 11674 Views: 7,094	Lists of NTIDs Post reply
	Dear kvgreddy06 Please have a look on this link. As far as I understood the 90%CI has to be within the acceptance range of 80-125%. Kind regards Dan — Kind regards and have a nice day Dr_Dan