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Hi,
I was wondering if it is possible to estimate the dose reduction by
direct delivery of antibiotics to the lungs.I mean from theoretical
point of view, how can we decide dose required to be administered
through inhalations when the oral and intravenous dose are known, and
what is the maximum dose which could be delivered to the lung.
Kind regards,
Shade
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The following message was posted to: PharmPK
Dear Shade,
Simulations Plus is in the process of adding the simulation of
nasal-pulmonary delivery of drugs to our top-ranked GastroPlus PBPK
software
under a funded collaboration with a top 5 pharmaceutical company. The
model
that we already have in internal testing provides a full PBPK
simulation of
drug absorption and distribution from a variety of dosage routes,
including
simulation of populations of specified mixes of ages, gender, and
Western/Asian physiologies. We expect to release this capability in the
coming months. With it, you should be able to estimate dose
requirements to
achieve either target plasma or tissue concentration levels, including
the
effects of a variety of factors such as particle size distributions,
inhalation methods, etc.
Please contact us if you would like to discuss the kinds of input data
you'd
need to make the dose estimate you mentioned.
Best regards,
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
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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Dear Shade,
Regarding delivering antibiotics to the lungs,
If you mean for treatment of the lungs, this is considered a topical
application.
Regards,
Frank Bales, Ph.D.
Email: frankbales.-at-.msn.com
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The following message was posted to: PharmPK
Dear Shade,
under
http://www.systems-biology.com/casestudies.html
you can find a poster presentation about a project with an inhalative
formulation of ciprofloxacin.
http://www.systems-biology.com/fileadmin/user_upload/sat_pages/PK-Sim/Presentations/Stass_2009_-_Cipro_Inhale.pdf
A major part of the story is about local exposure and the targeting
effect of
inhalation as compared to other routes of administration. Combined
with MICs you
can usually support dose adjustment considerations quite well. We use
the
approach in two iterations. 1) prediction of exposure and 2) analysis
of local
deposition based on the mechanistic physiologically-based model. The
calculation
of pulmonary exposure is done using PK-Sim and MoBi from our PBPK
modeling
platform. In a similar way we have already applied the methodology to
other IH
development candidates both in the antibiotics field and in other
pulmonary
indications (asthma, COPD...).
Since the platform supports predictive population modeling in special
populations like children, renally impaired, cirrhotics etc. you can
also
perform extrapolation tasks and regulatory feedback for M&S studies
especially
in the pediatrics arena (in support of PIP and PDP) has been very
positive.
Best regards
Joerg
P.S. Access to the software platform is free of charge for academic
partners
(non-profit projects and education). If there is interest from your
department
at Trinity just contact me or info.-at-.systems-biology.com.
--
Dr. Joerg Lippert
Head of Systems Biology & Computational Solutions
Bayer Technology Services GmbH
Leverkusen, E 41
Phone: +49 214 30 54813
Fax: +49 214 30 64801
E-mail: joerg.lippert.-at-.bayertechnology.com
Web: http://www.systems-biology.com/
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