Dear colleagues,Back to the Top
Could you tell me how to calculate PK parameters such as kel, CL and Vd
if
only data on multiple dosing (SS is reached) are available. Also, which
conc. should be used for calculation of PK parameters (such as AUC in
SS)-measured one (Cmin-just before the administration of the next dose)
or
Cav. If Cav should be used, how to calculate it?
Thanks a lot,
Anita
Dear Anita,Back to the Top
Analysis of data after multiple doses, or at steady state, can be done
by
most pharmacokinetic programs. If your program does not include the
steady-state option directly, you may need a 'trick': Enter a dosing
schedule of N doses with interval tau, and give your measurements time
points in the last interval, i.e. by adding (N-1).tau to the time
values. If
N is chosen sufficiently large, steady-state conditions will be met;
i.e.
(N-1).tau should be 10.t1/2 to be at 99.9% of steady-state.
If you do not have a suitable program, I can send you my program
MultiFit.
The optimal time points for the estimation of the pharmacokinetic
parameters
is a rather complicated question. There are special programs for this
purpose. As a rule of thumb, you need some measurements during the
absorption phase(in case of extravascular dosing only), some
measurements
during the elimination phase, and some around the expected peak time. In
short, the characteristics of the profile must be reflected in the
measurements.
The average concentration can be calculated from its definition as Cav AUC(0-tau) / tau (at steady state).
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.at.farm.rug.nl
Dear Anita,Back to the Top
In my previous message I did not mention that the program MultiFit also
allows a population analysis using an Iterative Two-Stage Bayesian
approach, a simple and very fast technique. The program is primarily useful for
research.
For patient-oriented applications I recommend the program MW\Pharm, that
uses the same algorithms. The latter program can be obtained from
Mediware at info.-at-.mediware.com. Both programs are running under DOS, but a Windows version of MW\Pharm is expected towards the end of the year.
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.aaa.farm.rug.nl
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)