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Dear all,
I want to asses pharmacokinetic interactions between the association
(Drug A + Drug B) and assets separate. The best statistical design?
(Drug A + Drug B) x Drug A x Drug B
Or
(Drug A + Drug B) x Drug A
(Drug A + Drug B) x Drug B
And more,
Should I evaluate bioequivalence or there is another method to asses
interactions between drugs???
Regards,
Bernardino Silva
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The following message was posted to: PharmPK
HI,
I am bit surprised when you asked about bioequivalence for
pharmacokinetic interaction study. I feel the group can answer this much
better if you could clarify my below question:
What is the aim of this study? Unless the aim is clear, it would
be very hard to suggest which design is better
What stage is this study in? I ask this because unless both/one
of the drugs are marketed, what's the need of bioequivalence.
For evaluating interactions of Pharmacokinetic(PK) nature, You can
assess the difference between PK parameters mainly Cmax, AUC. This will
give indication of increase or decrease in concentration in plasma.
Regards,
Yousuf
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The following message was posted to: PharmPK
Dear Bernadino!
I am not sure what you mean by
> [...] pharmacokinetic interactions between the association (Drug A
+ Drug B) and assets separate.
Commonly PK interactions are assessed for bioequivalence in steady
state.
Since not only absorption, but also clearance may be affected you
should additionally check this metric.
See these guidelines:
FDA
http://www.fda.gov/cder/guidance/2635fnl.pdf
http://www.fda.gov/cder/guidance/6695dft.pdf
EMEA
http://www.emea.europa.eu/pdfs/human/ewp/056095en.pdf
http://www.emea.europa.eu/pdfs/human/ewp/29793108en.pdf
Health Canada
http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/drug_medi_int-eng.pdf
....and also these papers:
Ciminera JL, Bolognese JA and MH Gregg
The Statistical Evaluation of a Three-Period Two-Treatment Crossover
Pharmacokinetic Drug Interaction Study
Biometrics 43, 713-718 (1987)
Steinijans VW, Hartmann M, Huber R and HW Radtke
Lack of pharmacokinetic interaction as an equivalence problem
Int J Clin Pharm Ther Toxicol 29(8), 323-328 (1991)
Mueller H-J and U Gundert-Remy
The regulatory view on drug-drug interactions
Int J Clin Pharmacol Ther 32(6), 269-273 (1994)
Schall R, Hundt HKL and HG Luus
Pharmacokinetic characteristics for extent of absorption and clearance
in drug/drug interaction studies
Int J Clin Pharmacol Ther 32(12), 633-637 (1994)
Regards,
Helmut
- Ing. Helmut Schuetz
BEBAC - Consultancy Services for
Bioequivalence and Bioavailability Studies
Neubaugasse 36/11
1070 Vienna, Austria
e-mail helmut.schuetz.aaa.bebac.at
web http://bebac.at/
contact http://bebac.at/Contact.htm
forum http://forum.bebac.at
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