Varsha,
I assume you are talking about a heparin like anticoagulant which can be
expected to act almost immediately. Therefore you can reasonably assume
that the bioassay used to measure the anticoagulant is a measurement of
the active form of the anticoagulant.
Thus you may consider the "response values in u/mL" as "plasma
concentrations".
In order to make sense of the PK parameter units you should find a way
of translating the mass of the dose (e.g. mg) into the units used for
the bioassay. This is easy to do in vitro. You can then do the pop PK
analysis in the usual way e.g. using the simple PK ADVAN subroutines.
If however your anticoagulant has a delayed mechanism of action then
some additional modelling may be necessary but the need for that depends
on the details (what is the mechanism? what is the magnitude of the
delay -- secs, mins, hours, days, etc).
Nick
Varsha Mehta wrote:
Dera NMUSERS:
I have a dataset where an anticoagulant has been administered and the response measured as unils/mL. Due to the inherent difficulty associated with measuring plasma concentrations of this drug no such measurements are available. I am interested in determining the population PK of this agent and connecting the dose size to response.
Should I be using a linked PK-PD model? Can I use the response values in u/mL
instead of plasma concentrations? Which model in the NONMEM library should I
start with ADVAN 5 or 6?
Thanks in advance!!
Varsha
Varsha Mehta, MS(CRDSA), Pharm.D., FCCP
Clinical Associate Professor
Pharmacy, Pediatrics and Communicable Diseases
Clinical Pharmacist Neonatal Critical Care
University of Michigan
(O) 734-936-8985
(F) 734-936-6946
[email protected]
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