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Dear Members,
I am designing a study of conventional vs controlled release
formulation bioequivalence studies. In this study, twice daily
formulation will be compared with once daily formulation. In another
study thrice daily formulation will be compared with once daily
formulation.
I need to know about how to design the blood sampling time points for
these differenct formulation. In addition to this, i need to know
which are all the PK parameters will be analyzed as well as ANOVA for
this study?
Expecting your inputs..
Thanks and Regards,
Francis
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The following message was posted to: PharmPK
It would better to compare a CR Vs a CR but with different
manufacturers.
However where you are comparing a conventional vs CR ensure that the
dosing strenght is the same for both for instance if CR volunteers
are taking 400mgs single dose then conventional volunteers should
also take 400 mgs as single dose the you can comfortably take
samples after for istance 0.5,1,2,4,6,8,10.12, hours
Plot a graph of concentration versus time (conventional and CR) apply
trapezoidal rule to calculate AUC for CR and conventional calculate
comfortably the relative biovailability
s.o.o
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Dear Sidney,
Thanks for your input.
There is no comparator for the CR formulation.I have to go for CR Vs
immediate release formulation.
CR Vs Twice daily formulation as well as CR Vs thrice daily formulation.
Here, in CR formulation dosing will be done once for a period.where
as in the case of twice daily formulation, dosing will be done for
two times per period and three times dosing for thrice daily
formulation.
I need to know how to fix up the blood sampling time points and
details about ANOVA for this model.
Thanks and regards,
Francis
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Dear Francis,
I would like to suggest the following:
- use a different sampling schedule based on the formulation
(e.g. more frequent sampling for the immediate-release formulation
(IR) and may be less frequent for the CR)
- it is important to capture as accurate as possible the
Cmax of these formulations
- sampling beyond the 24 hours should be based on the half-
life of the drug
- use a 3-way crossover design with six sequences
- random allocation of the subjects to the 3 treatments: CR,
IR q12h and IR q8h
- there is no special model required in the ANOVA. Use
Subjects, Sequence, Treatment and Period as factors
If there are going to be too many missing data I
will like to suggest to use PROC MIXED and not GLM in SAS
- 2 or 3 studies will be needed:
- single-dose under fasting conditions
- single-dose under fed conditions
- multiple-dose studies
- evaluate the usual parameters: AUCt, AUCinf, Cmax, Tmax,
Kel, Half-life and MRT in single-dose studies
- evaluate the usual parameters: AUCtau, Cmax, Tmax, Cmin,
Fluctuation and Swing in multiple-dose study
Note1: the term-single-dose refers to the CR formulations. The IR
formulations will be administered twice or 3 times.
Note2: in the multiple-dose study collect trough levels up to the
steady-state and frequent sampling over 24 hours in the last day
I hope this helps.
radu
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The following message was posted to: PharmPK
For blood sampling points the bottom line is to ensure that the
biological half life of the drug is within the sampling points. For
controlled release drugs a 12 hour Experimental time is required
cause the assumption is that after 12 hours the drug is already in
the feaces or urine. However there is no limit to these you can even
go up to 36 hours.
For instance research in Uganda reveal that chloroquine conventional
tablets even after 36 hours it could still be detected in the blood.
Later on ministry of health change the dosage from 2 t.ds to. 4.4.2
ie four on the first day four on the second day then two on the third
day
Sampling time example for instance im currently doing some work on
ibuprofen
the biological half life of ibuprofen is 2 hours
For Biovailability studies my blood sampling points would be
0.5,1,1.5,2,3,4,6,8,10,12,16,20,24etc
The reason for these is that at the end of the study you have
calculate all the Biopharmaceutic and pharmacokinetic parameters. For
instance AUC, Tmax,Cmax,Kel,Ka t1/2 etc ie you are killing two birds
with one stone
s.o.o
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)