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What is the protocol for a multi-dose bioequivalence study?
I must to administrate only the reference (or test) product until it
reaches
steady-state concentration and monitoring its conc-time profile …and
later, the
same protocol for another product….
Or
I administrate a product until it reaches steady-state concentration, I
administrate the reference product (monitoring C/time) and next, the
test
product. In this case, how can I calculate the AUC for an interval of
dosing?
Using real values for conc (AUC total) or differences (conc
observed-conc 0)?
Thank you
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Hi Vlase,
Based on the data from your e-mail it appears that you are interested
in a bioequivalence study.
The usual approach is one single protocol with the following phases:
Period 1 - dose one of the drug-products until it reaches the
steady state. During this phase pre-dose samples are collected as
evidence for the increase in concentration levels and
finally in achieving the steady-state. At least 3 pre-dose levels
collected at steady-state are needed for the
statistical analysis of these data.
- detailed sampling over one dosing interval to obtain
good estimates for Cmax, Tmax, Cmin and AUCtau. Derived parameters may
be swing and/or fluctuation.
- washout for the elimination of the drug/metabolites
from the body
Period 2 - dose the second (usually randomly selected) of the
drug-products until it reaches the steady state. During this phase
pre-dose levels are collected as evidence for the
increase in concentration levels and finally in achieving the
steady-state. At least 3 pre-dose levels collected at
steady-state are needed for the statistical analysis of these data.
- detailed sampling over one dosing interval to obtain
good estimates for Cmax, Tmax, Cmin and AUCtau. Derived parameters may
be swing and/or fluctuation.
Analysis of variance of the steady-state pre-dose levels should show no
statistically significant TIME effect and no TIME-by-TREATMENT
interaction. The first is the proof of achieving steady-state and the
second of no difference between treatments in the drug accumulation if
a slight upward trend is still present.
Once the steady-state is proven the PK parameters are then analyzed
with the usual model as for any other bioequivalence study.
I hope this help,
radu
Radu D. Pop
Director Biopharmaceutics
Pharma Medica Research Inc.
966 Pantera Drive
Mississauga, Ontario
Canada, L4W 2S1
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)