- On 13 Jan 1999 at 14:16:14, "Julia Emelogu" (jemelogu.aaa.un13.freeserve.co.uk) sent the message

Back to the Top

Dear Colleagues,

I am a Ph.D. student trying to design and validate a physiologically based

pharmacokinetic-pharmacodynamic model following inhaled/intracheal

administration in rat, monkey, or any another species, as well as in humans

to be extrapolated to human and pathological disease state, i.e. asthma

and/or cystic fibrosis.

However I am having difficulty finding the relevant data for the model

building methodology.

Does any one have or know where I can find raw data of the following:

Drug concentrations/amounts in blood, lung and any other organs, and any

related pharmacodynamic data for the following groups of drugs, following

intratracheal/inhaled administration:

Glucocorticoids: Budesonide, Fluticasone Propionate,

Aminoglycosides: Gentamicin, Tobramycin, etc

Any assistance would be greatly appreciated

J. Emelogu

Dear Colleagues,

I am a Ph.D. student trying to design and validate a physiologically

based pharmacokinetic-pharmacodynamic model following

inhaled/intracheal administration in rat, monkey, or any another

species, as well as in humans to be extrapolated to human and

pathological disease state, i.e. asthma and/or cystic fibrosis.

However I am having difficulty finding the relevant data for the model

building methodology.

Does any one have or know where I can find raw data of the following:

Drug concentrations/amounts in blood, lung and any other organs, and

any related pharmacodynamic data for the following groups of drugs,

following intratracheal/inhaled administration:

Glucocorticoids: Budesonide, Fluticasone Propionate,

Aminoglycosides: Gentamicin, Tobramycin, etc

Any assistance would be greatly appreciated

J. Emelogu - On 16 Jan 1999 at 23:45:15, David_Bourne (david.-a-.pharm.cpb.uokhsc.edu) sent the message

Back to the Top

[Two 'replies' - db]

Date: Fri, 15 Jan 1999 23:49:00 -0500

From: jliu

X-Accept-Language: en

MIME-Version: 1.0

To: PharmPK.-at-.pharm.cpb.uokhsc.edu

Subject: Re: PharmPK Pharmacokinetic data

You are asking too much. If someone has all these raw data, why bother you

to build a model?

---

X-Originating-IP: [202.54.84.179]

From: "LAXMIKANT SUGANDHI"

To: PharmPK.-a-.pharm.cpb.uokhsc.edu

Subject: Re: PharmPK Pharmacokinetic data

Date: Sat, 16 Jan 1999 02:53:04 PST

Mime-Version: 1.0

this question is troubling me for a long time

please mail if u get

thanks in anticipation

l.p.sugandhi - On 18 Jan 1999 at 09:55:10, Maria Durisova (exfamadu.aaa.savba.savba.sk) sent the message

Back to the Top

Daer colleague,

In our study:

Durisova M., Dedik L., Balan M.: Bull. Math. Biol., 57,

1995, 787-808,

we presented a new method (based on a combination of system modeling

in the frequency and time domain)

for building structured models permitting

physiological interpratation. We used this mothod in the study

of the system describing gentamicin bioavailability after

intratracheal administration in guinea pigs. The model selected

in this study indicated

four fractions of gentamicin with different pahtways

into the blood circulation. Furthermore, the model

allowed to quantify these fractions

and to determine the values of the mean resindence time corresponding

to these fractions.

The method presented in our study metioned above

can be used without any a priori information or assumptions

(e.g. those typical for compartment models), utilizing exclusively

a posteriori knowledge about the system under study provided

by experimental measurements.

However, if a priori information about the system under study

is available it can be used in this method. Except for

linearity the method is totally independent.

If you are interested in this method or in the experimental

data, do not hesitate and let me know.

Sincerely,

Maria Durisova - On 23 Jan 1999 at 20:32:11, Maria Durisova (exfamadu.-at-.savba.savba.sk) sent the message

Back to the Top

> Hi, would you please to give me the detail method? Thanks.

O.K.

A short description of the basic steps of the method based on

a combination of system modeling in the frequency and time

domain, used in our study Durisova M., Dedik L., Balan M.,

Bull. Math. Biol., 57, 1995, 787-808, is as follows:

1. System definition.

The system describing gentamicin bioavailability after

intratracheal administration to guinea pigs (thereafter the

system) was defined by the output/input form of its transfer

function H(s)

H(s)=C_it(s)/C_iv(s),

using the deterministic circulatory model presented in our

study (Comput. Meth. Programs Biomed., 51, 1996, 183-192).

C_it(s) and C_iv(s) were the Laplace transforms of the

gentamicin concentration profiles in plasma C_it(t) and

C_iv(t) after intratracheal and intravenous administration,

respectively.

2. System modeling in the frequency domain.

The software package CXT described in our study (Int. J.

Bio-Med. Comput., 39, 1995, 231-241) was used to model the

system in the frequency domain and to obtain the inverse

transformations of the results in the time domain.

The model obtained in the frequency domain and the model

weighting function determined in the time domain indicated

the presence of time delays in the system. With the regard to

these results, the whole frequency band of the frequency

domain model was separated into the two bands: 1) the

low-frequency band in which the influences of system time

delays could not be identified by the naked eye; 2) the

high-frequency band in which these influences were distinct.

In the low-frequency band, the system was approximated by

various low-order auxiliary models without time delays, using

the CXT program.

The auxiliary models whose outputs were similar to the measured

output of the system (i.e. C_it(t) profile) were considered

the suitable auxiliary models of the system in this frequency

band. In the high-frequency band, the system time delays were

estimated.

3. System modeling in the time domain.

Various structured models with different arrangements of the

suitable auxiliary models selected in the low-frequency band

and the models containing the time delays estimated in the

high-frequency band were created and described by sets of

differential equations. Outputs of these models were obtained

as their responses to the measured input of the system (i.e.

C_iv(t) profile), by fitting these models to the measured

output of the system (i.e. C_it(t) profile), using the

Gauss-Newton method. Weighting functions of the structured

models were determined as responses of these models to the Dirac

delta pulse. Eventually, a group of the structured models was

selected in which all the models had the estimates of the

standard errors of their parameters less than 50% of the

corresponding parameter estimates, and simultaneously the

outputs and weighting functions of these models were similar

to the output and weighting function of the model determined

in the frequency domain (see step 2). The structured model

with the minimum value of the Akaike criterion was selected

in this group and considered the final structured model of

the system.

4. Determination of MRTs.

The transfer function of the final structured model was

derived using the system approach rules in the Laplace

domain. This transfer function subsequently was used to

derive the formulae for MRTs. Employing these formulae and the

parameter estimates of the final structured model, the MRTs

were determined.

Best regards,

Maria Durisova

Want to post a follow-up message on this topic? If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Pharmacokinetic data" as the subject

PharmPK Discussion List Archive Index page

Copyright 1995-2010 David W. A. Bourne (david@boomer.org)