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Dear Colleagues,
In the field of drug targeting, PK and PK/PD modeling do not seem
to be used often.
Does anybody know some papers on this subject? E.g. describing
modeling theoretically or based on experimental data, or dealing
with the subject in relation to possibilities and limitations?
Or do you have an opinion about this topic?
I would be grateful for any suggestion.
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.-a-.farm.rug.nl
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Date: Thu, 1 Jul 1999 09:09:26 -0400
To: PharmPK.at.boomer.org
From: Daro Gross
Subject: Re: PharmPK PK modeling in drug targeting
I spent the past 13 years developing PK/PD drug targeting models. Most of
them flopped. But the last one seems to be working better than could be
expected. Some parts of the model are simple to understand and work with.
However, the model itself came as a surprise so you may ask any questions
you may have, but the papers will have to wait until enough research has
been conducted to verify the techniques used according to standard medical
research methods: the model advocates methods of calculating drug targeting
that can only be described as "cross-disciplinary" (i.e., information from
all areas of medicine are required for accurate prediction).
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From: giandomenico.brogin.at.zambongroup.com
To: PharmPK.-a-.boomer.org
Date: Thu, 1 Jul 1999 16:39:04 +0200
Subject: Re: PharmPK PK modeling in drug targeting
Mime-Version: 1.0
Hello Johannes,
few references on "drug targeting":
- Stella, V. J. "Prodrugs and site-specific drug delivery"
J. Med. Chem. 23: 1275-1282, 1980
- Takakura Y. "Macromolecular carrier systems for targeted drug delivery:
pharmacokinetic considerations on biodistribution"
Pharmaceutical Research 13: 820-831, 1996
- Stella, V. J. and Kearney, A. S. "Pharmacokinetics of drug targeting:
specific implications for targeting via prodrugs".
In R .L. Juliano (ed.), Targeted drug delivery (Handbook of Experimental
Pharmacology vol. 100), Springer-Verlag, Berlin Heidelberg, 1991, pp.
71-103
Hope this helps
Giandomenico Brogin
e-mail : giandomenico.brogin.at.zambongroup.com
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My group has done some work in the PK/PD assesment of pulmonary
targeting using animal models and theoretical approaches. The following
references might be of some interest for you.
Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using
glucocorticoids as a model, G. Hochhaus, H. Derendorf, H. M=F6llmann, R.
Gonzalez-Rothi. J. Clin. Pharmacol. 37, 881-892 (1997)
Pharmacokinetic/pharmacodynamic correlation of pulmonary and cardiac
effects of fenoterol in asthmatic patients after different routes of
administration. G. Hochhaus, E.W. Schmidt, K.L. Rominger, H.W. M=F6llmann.
Pharm. Res. 9, 291- 297 (1992)
Effect of dose and release rate on pulmonary targeting of liposomal
triamcinolone acetonide. S. Suarez, R.J. Gonzales-Rothi, H. Schreier, G.
Hochhaus. J. Pharm. Res., 15, 461-465 (1998)
Pulmonary targeting of inhaled glucocorticoids: How is it influenced by
formulation? G. Hochhaus, S. Suarez, R.J. Gonzales-Rothi, H. Schreier,
Respiratory Drug Delivery VI, R. Dalby, P. Byron, S.J. Farr, eds,
Interpharm Press, Buffalo Grove, IL (1998), 45-52.
I also recommend articles from Tony Hunt which he published in 1986 (I
don't remember the journal), Rowland et al., J Pharmacokinet Biopharm
24, 369 (1996); Sieget et al. J Pharmacokinet Biopharm 19, 363 (1991)
Hope this information is helpful.
Guenther Hochhaus
Associate Professor
College of Pharmacy
University of Florida
Gainesville, FL,32610
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[Two replies - db]
Alternate-recipient: prohibited
Date: Thu, 01 Jul 1999 10:03:56 -0400 (EDT)
From: Meyer Katzper 301-827-2514 FAX 301-827-2531
Subject: RE: PharmPK PK modeling in drug targeting
To: postmaster
Posting-date: Thu, 01 Jul 1999 10:29:00 -0400 (EDT)
Importance: normal
Priority: normal
A1-type: MAIL
The topic you have brought up for discussion,
PK and PK/PD modeling in the context of clinical trials deserves some critical
attention. A major factor to be addressed is PD variability. Gerhard Levy has
published a number of papers on this topic. I agree with his outlook that many
more biochemical and physiological factors must be collected. The current small
number of demographic variables do not form a sufficient basis for obseved
variability. Current thinking and trial design is based on crude compartmental
and population modeling. These are an insufficient conceptual framework for
advancing our understanding of individual variability.
Meyer Katzper, Ph.D.
FDA/CDER
E-mail katzper.-a-.cder.fda.gov
Tel (301) 827-2563
Fax # (301) 827-2531
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Alternate-recipient: prohibited
Date: Thu, 01 Jul 1999 09:53:35 -0400 (EDT)
From: Elena Mishina 301-594-0496 FAX 301-480-3212
Subject: Re: PharmPK PK modeling in drug targeting
To: postmaster
Posting-date: Thu, 01 Jul 1999 09:53:36 -0400 (EDT)
Importance: normal
Priority: normal
Sensitivity: Company-Confidential
A1-type: MAIL
I have done some work in this field. If you would be interested you can
look up the following papers.
We have developed a new formulation of methylprednisolone designed to
target the immune system, particularly, spleen, measured PK and PD (effects
on glucocorticoid receptor density and suppression of splenocyte
proliferation ex vivo) and modeled PK and PK/PD in comparison with
conventional formulation.
Mishina E. V., Straubinger R. M., Pyszczynski N. A., Jusko W.J. Enhancement
of tissue delivery and receptor occupancy of methylprednisolone in rat by a
liposomal formulation. Pharm. Res. 1993, 10, p. 1402-1410.
Mishina E. V., Pyszczynski N. A., Jusko W.J. Inhibition of rat splenocyte
proliferation with methylprednisolone: in vivo effect of liposomal
formulation. Pharm. Res. 1994, 6, 848-854.
Mishina E. V., Jusko W.J. Selected tissue distribution of liposomal
methylprednisolone in rat. Res. Com. Chem. Path. Pharmacol, 1994, 84 (1)
47-52.
Mishina E. V., Binder J., Kupiec-Weglinski J., Jusko W.J. Effect of
liposomal methylprenisolone on heart allograft survival and immune function
in rat. J. Pharm. Exp. Ther., 1994, v. 271(2), p. 868-874.
Binder J., Mishina E. V., Jusko W.J., Kupiec-Weglinski J. Prolongation of
cardiac allograft survival in rats by liposome-encapsulated
methylprednisolone. Transplantation, 1994, 58 (5) 633-635.
Mishina E. V., Binder J., Jusko W.J., Kupiec-Weglinski J.W.
Liposome-encapsulated methylprednisolone enhances drug delivery to host
tissues and prolongs the survival of cardiac allograft in rats.
Transplant. Proc., 1996, 54.
Mishina E. V. and Jusko W.J. Liposomal methylprednisolone in rat:
dose-proportionality and chronic-dose pharmacokinetics/pharmacodynamics.
Pharm. Res., 1996, 13: 141-145.
Best regards,
Elena Mishina,
Pharmacometrics, CDER, FDA
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)