RE: Model estimate of dose

From: "Nick Holford" n.holford@auckland.ac.nz Subject: RE: [NMusers] Model estimate of dose Date: Mon, November 29, 2004 1:53 pm Johan, I have some difficulty understanding what you are trying to do. The situation is exactly comparable to giving a parenteral bolus dose into the central compartment and measuring drug in the central compartment and the peripheral compartment (with elimination from the peripheral compartment). In this situation one would not typically try to estimate bioavailability. It would be assumed to be one. The dose is usually treated as a known quantity in pharmacokinetics. If the amount reaching the systemic circulation is less than the dose then it is usual to estimate the extent of bioavailability. This can be done easily by estimating F1, the bioavailability fraction for a dose entering compartment 1 (assuming this is where you have put the dose specified by the AMT data item). In your case if you have some other data e.g. concentrations after a parenteral dose to the central compartment then under the usual assumption that clearance does not change then you can estimate F1 by fitting the two sets of data simultaneously. Unlike the usual oral plus IV dose experiment, because you have absorption compatment concs you will be able to estimate the apparent volume of the absorption compartment in addition to other parameters such as KA. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/