Re: NMUSERS-modeling dose and response

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] > > ********************************************************** > Electronic Mail is not secure, may not be read every day, and should not be > used for urgent or sensitive issues -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford