From kyungsoo Mon Sep 16 11:49:09 1996
Subject: new program

Dear NONMEM users:

We have developed a program to estimate model-independent pharmacokinetic parameters (MIPK) such as area under concentration-time, peak concentration and time to peak concentration for noisy population PK data from a sparsely sampled designed trial. The program is implemented within the mixed-effect model framework in order to be used as a user-supplied subroutine to NONMEM, with applications to the single-dose and steady-state case. It can be used in both UNIX and PC environments.

To describe individual concentration vs time, the program adopts a semiparametric model involving a longitudinal spline, which is constrained to exhibit (i) decreasing tail (ii) typical Tpeak near the data-based population modal Tpeak, and (iii) value = zero at time = zero (single-dose), or the same non-zero value at the beginning and end of a dosing interval (steady-state). We call the resulting splines Constrained Longitudinal Splines (CLS). Details are found in a paper coming out, and we will let the interesting user know the reference when it is accepted.

In addition to individual MIPK estimates obtained from an individual's CLS, the program also yields estimates of the typical MIPK values for a typical individual.

The files for the program are available in directory NONMEM.DIR/CLS.DIR by anonymous ftp from the NONMEM repository or from the NONMEM users network:



Kyungsoo Park, Davide Verotta, and Lewis B. Sheiner
University of California, San Francisco
Room C255, Box 0626
San Francisco, CA 94143