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Dear all
I have a query. I am interested in carrying out PK and PD
bioequivalence study of two test formulations with the reference
formulation. The dose of the drug is 240 mg once a day. But my
limitation is that the 240 mg formulation is not available in the
market currently. Can i give the volunteers two tablets of 120 mg SR
tablets, will it be equivalent to 240 mg
Please suggest. this study is for research purposes and not for any
regulatory submission.
Regards
Tausif Ahmed
Doctorate student, Dept. of Pharm. Medicine
Ranbaxy CPU, Hamdard university
Delhi, India
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Dear Tausif
Yes, you can do this study based on limited information given by you.
It seems you are converting multiple dose into a OD formulation. Based
on this assumption you need to do single dose and steady state studies
including food effect.
In any case you will have to see toxic effects of normal and overdose.
The answer to your question also depends upon which class the molecule
belongs to. If it is alpha blocker or SNRI you have to convince IEC
with a very strong rationale.
Thanks and regards
Dr. Prashant
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The following message was posted to: PharmPK
Hi Tausif
It is my opinion that you cannot use two 120 mg slow
release (SR) tablets as substitutes for a 240 mg
tablet unless the original reference formulation was a
slow release preparation as well. Are your new
formulations normal or slow release tablets? May be
other contributors may have a different view.
Thank you.
F.A. Ogunbona, B.Pharm., Ph.D.
Dept. of Pharm. Chem
Faculty of Pharmacy
Obafemi Awolowo University, Ile-Ife
Nigeria
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Hi Ogunbona
Well the 120 mg tablets I am planning to use are SR tablets only.
Bye
Tausif
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Dear Prashant
Thanks for your reply.
Well I am working on diltiazem. In market at present no 240mg
formulations are available. We are interested in doing single and
multiple dose Pk/PD studies.
Can wegive 2 120 mg SR tablets as a substitute of one 240 mg tablets.
I think I have mademyself clear
Regards
Tausif Ahmed
Ph.D. Scholar, Dept. of Pharm. Medicine
Ranbaxy CPU, Majeedia Hospital,
Hamdad University
New Delhi
India
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The following message was posted to: PharmPK
As far a diltiazem is concerned there is much in the literature to
suggest
that the
ordinary tablets behave in a different way to the or modified release
formulations. In the UK there are a number of 240 mg avalable.
Furthermore
the British National Formulary suggests that once started on one
formulation
of modified release that it should not be switched. This means that if
you
are making comparisons you need to very careful of the formaulations
being
used.
Best wishes
Graham Mould
Guildford Clinical Pharmacology Unit
Royal Surrey County Hospital
Guildford
UK
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Here are a number of web sites with information on diltiazem:
http://www.rxlist.com/cgi/generic/diltiaz_cp.htm
http://www.cipla.com/ourproducts/04/dilgard.htm
http://courses.washington.edu/pharm560/Spring_Pharm562_2001/TXDrugIn.pdf
http://www.anaesthetist.com/physiol/basics/metabol/cyp/d.htm
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/
query?uid=9223567&form=6&db=m&Dopt=b
and a few other notes:
Ritschel
t 1/2 = 4h
Kel = 0.173 / h
Vd = 0.77 L/kg
CL = Kel*Vd = 0.1332 L/h/kg
F = 0.5
EPB = 80%
Ther range 0.03-0.02 ug/mL
Dose = 60 mg
Tmax = 1.5 h
Lave et al Pharm Res 14:152-155
C=2-20 umol
CLint(in vitro) = 0.36-0.83 uL/min/10^6 cells
Obs Eh = 0.03 (calculated from hepatic blood CL)
Ekins & Obach J. Pharmacol & Experimental Therapeutics 295:2:463-473
CLint hepatocytes 1.62 ul/min/10^6 cells
Obach Drug Metabolism Dispos 27:1350-1359 (1999)
CLint microsomes = 15 +/- 2 ml/min/kg
CLint hepatocyes = 6.2 ul/min/10^6 cells
Best regards,
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (SIMU)
1220 W. Avenue J
Lancaster, CA 93534-2902
U.S.A.
http://www.simulations-plus.com
Phone: (661) 723-7723
FAX: (661) 723-5524
E-mail: walt.at.simulations-plus.com
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The following message was posted to: PharmPK
Dear Tausif
Thanks for additional piece of information.
Yes you can give two 120 mg SR formulations to compare it with a
240 mg formulation. Still i wouldnot advice it because, 240 mg ER
is available in the market. Please check Tiazac 240 mg Capsule by
Forest, Cardizem CD 240 mg by Aventis are listed in PDR. In such a
case to avoid any questions by regulators it is better to use 240
mg formulation.
Thanks and Regards
Dr.Prashant
Ph.D.
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