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Back to the forum  Query: 2018-05-20 11:57 CEST (UTC+2h)
 
Inder
Junior

India,
2018-05-12 09:31

Posting: # 18761
Views: 279
 

 BABE for Cefixime Tablets - Canada [Design Issues]

Hello all,

Can anyone please confirm, for (generic) Cefixime tablets, do we need to submit both, Fasting and Fed BE studies in Canada?

As far as i know, we submit Fasting studies for most of the products (uncomplicated IR products) in Canada.

However, somewhere on google, i found an article stating that Cefixime has non-linear kinetics. Therefore, i am not sure if we need to conduct both fasting and fed or only fasting will be fine.

A quick response is really desired.


Thanks,
Inder


Edit: Relax; see also this post #9. Please don’t shout[Helmut]
lakshmiprasad
Junior

India,
2018-05-14 07:13

@ Inder
Posting: # 18762
Views: 202
 

 BABE for Cefixime Tablets - Canada

hi,

good morning,

As per canadian guidelines the fasting and fed study was required for only modified formulations. So, I think we can go with fasting study and I was checked literature i didnt find any non-linear things in kinetics. So, my suggestion is fasting study.


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 #5[Helmut]
Inder
Junior

India,
2018-05-17 08:13
(edited by Ohlbe on 2018-05-17 10:08)

@ lakshmiprasad
Posting: # 18772
Views: 93
 

 BABE for Cefixime Tablets - Canada

Thanks a Lot Lakshmiprasad...


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! [Ohlbe]
Helmut
Hero
Homepage
Vienna, Austria,
2018-05-17 12:11

@ lakshmiprasad
Posting: # 18773
Views: 83
 

 Nonlinear PK (less than proportional increase in AUC): lowest strength

Hi Lakshimi,

» As per canadian guidelines the fasting and fed study was required for only modified formulations.

It still is! Comparative Bioavailability Standards: Formulations Used for Systemic Effects, Section 2.1.1.1 (2012):

Requirements for modified-release dosage forms differ from those for immediate-release formulations because a greater likelihood exists that increased inter-subject variability in bioavailability will occur, including the possibility of dose-dumping. There may also be an increased risk of adverse effects such as gastrointestinal irritation, depending on the site of drug release, or absorption, or both. Hence, for all modified-release dosage forms (including delayed-release formulations), bioequivalence should be demonstrated under both fasted and fed conditions.


» So, I think we can go with fasting study …

Correct, since the tablets are IR.

» … and I was checked literature i didnt find any non-linear things in kinetics.

Maybe you should improve your skills in literature research.1–5
Click here ⇒  :google: or there ⇒ Google Scholar

HC’s guidance, section 2.1.1.3:

For drugs with non-linear pharmacokinetics in the single unit dose range of approved strengths due to saturable absorption and resulting in less than proportional increases in AUC with increasing dose, the comparative bioavailability study should be conducted on at least the lowest strength (single dose unit).



  1. Brittain DC, Scully BE, Hirose T, Neu HC. The pharmacokinetic and bactericidal characteristics of oral cefixime. Clin Pharmacol Ther. 1985;38(5):590-4. doi:10.1038/clpt.1985.229.
  2. Faulkner RD, Fernandez P, Lawrence G, Sia LL, Falkowski AJ, Weiss AI, Yacobi A, Silber BM. Absolute bio­availability of cefixime in man. J Clin Pharmacol. 1988;28(8):700-6. doi:10.1002/j.1552-4604.1988.tb03203.x.
  3. Guay DRP, Meatherall RC, Harding GK, Brown GR. Pharmacokinetics of Cefixime (CL 284,635; FK 027) in Healthy Subjects and Patients with Renal Insufficiency. Antimicrob Agents Chemother. 1986;30:485–90. free resource.
  4. Klepser ME, Marangos MN, Patel KB, Nicolau DP, Quintiliani R, Nightingale C. Clinical Pharmacokinetics of Newer Cephalosporins. Clin Pharmacokin. 1995;28(5):361–384. doi:10.2165/00003088-199528050-00003.
  5. Nix DE, Symonds WT, Hyatt JM, Wilton JH, Teal MA, Reidenberg P, Affrime MB. Comparative Pharmaco­kinetics of Oral Ceftibuten, Cefixime, Cefaclor, and Cefuroxime Axetil in Healthy Volunteers. Pharmacother. 1997;17(1):121–5. doi:10.1002/j.1875-9114.1997.tb03684.x.

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