- On 30 Dec 1999 at 20:33:33, David_Bourne (david.-a-.boomer.org) sent the message

Back to the Top

[Two replies - db]

Date: Thu, 30 Dec 1999 01:52:17 -0700 (MST)

X-Sender: ml11439.at.pop.goodnet.com

To: PharmPK.-at-.boomer.org

From: ml11439.aaa.goodnet.com (Michael J. Leibold)

Subject: Re: PharmPK Re: Statistical description of tmax

Hello Osama,

Regarding FDA Bioequivalence [the -20%/+25% rule]

I visited the FDA web site and read the FDA orange book and took

some notes. According to the FDA orange book, the FDA considers drugs

to bioequivalent if :

1) The rate and extent of absorption of the test drug to not differ

significantly from that of the reference drug.

2) The extent of absorption of the test drug does not differ significantly

from that of the reference drug and the difference from the reference drug

in the rate of absorption is intentional, is reflected in the proposed

labeling of the test drug, and is not essential to the attainment of

effective body concentrations and is considered medically insignificant

for the drug.

Statistical Criteria for Bioeqivalence

Bioequivalence of the test and reference drugs involves equivalence with

respect to the extent and rate of absorption. AUC (extent) and Cmax (rate)

are log-transformed for parametric statistical analysis where 90% confidence

intervals are computed for the mean of each log transformed parameter. The

90% confidence interval must be within 0.8 and 1.25 times that of the mean

of the reference drug. This is the -20%/+25% rule which means that if the

mean log-transformed parameter is close to -20% or +25% of the mean of the

log-transformed reference drug parameter, then the confidence limits are

likely to fall outside this range, and the test drug will not be bioequiva-

lent. Since the 90% confidence interval is two tailed, if it is within 0.8-

1.25 times the reference mean, there is only a 5% chance that the test drug

mean violates the -20%/+25% rule and might not be bioequivalent.

Evidently, other pharmacokinetic parameters reflecting extent and rate

of absorption may be used as implied by the terms "bioequivalence parameters

such as AUC or Cmax".

Therapeutic Equvalence verus Bioequivalence

The FDA classifies drugs as "therapeutically equivalent" if:

1) They are approved as safe and effective

2) They are pharmaceutical equivalents (same active ingredient)

3) They are "bioequivalent"

4) They are adequately labeled

5) They are manufactured with Current Good Manufacturing Practice

Mike Leibold, PharmD, RPh

ML11439.-at-.goodnet.com

---

X-Sender: flerner.aaa.mail.intramed.net.ar

Date: Thu, 30 Dec 1999 08:21:55 -0300

To: PharmPK.-at-.boomer.org

From: Federico Ezequiel Lerner

Subject: Re: PharmPK Re: Statistical description of tmax

Dear all

For several kinetics parameters of some drugs is imposible to have log

normal distribution the example of that is drugs with different metabolic

pathway as fluoxetin that shows two kind of populations. so parametric

analyses is not appropriate.

Regards and best wishes for the new year

Federico Lerner - On 31 Dec 1999 at 18:35:38, exfamadu.at.savba.sk sent the message

Back to the Top

Rate of the drug bioavailability is a function of time, not a constant

parameter. This function can be determined in a numerical and/or

analytical form. In our study (Durisova M. and Dedik L. Pharm. Res. 14,

1997, 860-864) we introduced a criterion which can be used for testing

equivalence of two rates of the drug bioavailability from two different drug

fromulations. The criterion is based on the weighting functions determined

in analytical forms.

With best wishes for the new year

Maria Durisova

Dr. Maria Durisova Ph.D.

Senior Research Worker

Scientific Secretary

Institute of Experimental Pharmacology

Slovak Academy of Sciences

http://kam.vm.stuba.sk/~dedik

SK-842 16 Bratislava

Slovak Republic

Want to post a follow-up message on this topic? If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Statistical description of tmax" as the subject

PharmPK Discussion List Archive Index page

Copyright 1995-2010 David W. A. Bourne (david@boomer.org)