The USC*PACK pharmacokinetic programs: New release, December 1, 2002

The Laboratory of Applied Pharmacokinetics of the USC School of Medicine is pleased to announce its new Version 11.7 of the USC*PACK programs for population pharmacokinetic modeling, modeling larger nonlinear systems, and for planning, monitoring, and optimal individualization of goal-oriented drug dosage regimens for patient care.

WHAT'S NEW IN THE SETUP! CLIENT - SERVER MODES

The programs now run in 3 modes. The first is the usual mode on a single machine. The second is on a network, in a classroom mode. Each classroom machine accesses the programs from the network, but keeps its patient data files in its own disk or directory. The third is a true client-server mode. Here, all programs and patient data files are kept on the central hospital server, for example, but are accessed and run from the satellite (client) machines.

WHAT'S NEW WITH AMINOGLYCOSIDES

These programs have several new population PK models, for general medical patients, ICU patients, young previously healthy patients, and for gentamicin in patients with spinal cord injuries and for newborn infants. As before, the GENTamicin, TOBramycin, NETilmicin, and AMIKacin programs compute D-optimal times for monitoring serum levels. Diffusion into vegetations and dynamics of bacterial growth vs killing effect at a stated MIC can also be evaluated as described just below.

WHAT'S NEW WITH GENERAL MODELING, BAYESIAN FITTING

The General Modeling, Bayesian fitting program has an option for entry of a chronic steady-state dosage regimen, followed by subsequent changes in dosage or renal function. Other related programs compute the dynamics of diffusion into a spherical simulated endocardial vegetation, abscess, or a bacterium, nonlinear saturable pharmacological effects, and the dynamics of bacterial growth and kill, and the post-antibiotic effect (PAE). These help to evaluate the efficacy of antibiotic regimens with respect to their ability to kill adequately under various circumstances, for various values of an organism's MIC. Models for simulating a PAE of 6 hours, and for growth and kill of Pseudomonas by gentamicin, tobramycin, and ticarcillin are now provided. You can also make and store your own models.

WHAT'S NEW WITH THE NPEM2 POPULATION MODELING PROGRAM

The NPEM2 program has been very much overhauled and upgraded. It now automatically helps you select an appropriate number of grid points to support your population joint density. It has algorithms to make each computational cycle go progressively faster. The 2D plots of the marginal and the 3D plots of the joint marginal densities are enhanced. Scatterplots and regression relationships are now available for predicted versus measured serum levels in both the Iterative 2 Stage Bayesian (IT2B) front population modeler, from mean or median population parameter values. Each patient's own Bayesian posterior parameter values can also be used to predict the measured levels. For the NPEM2 part, one similarly can predict measured serum levels from population mean, median, or mode values, and can also further compute each patient's parameter joint density as a "population" of one, and can see the predicted versus measured serum levels based now on each patient's own mean, median, or mode parameter values.

THE OVERALL USC*PACK COLLECTION NOW INCLUDES:

1. The USC*PACK CLINICAL programs. These enhance precise goal-oriented dosage design and therapeutic drug monitoring by Bayesian individualization of drug dosage regimens. Drugs include aminoglycosides, vancomycin, digoxin, digoxin with quinidine, digitoxin, lidocaine, procainamide, theophylline, quinidine, gentamicin in newborns, and TMP-SMX for PCP pneumonia. CCr is computed between a single stable or pairs of unstable serum creatinine levels. It can change from dose to dose, as can body weight. Models of diffusion and bacterial growth and killing are especially useful to evaluate adequacy of a regimen to kill under stated conditions of growth rate, max kill rate, and MIC.
2. The USC*PACK NPEM2 POPULATION pharmacokinetic modeling program employs a nonparametric expectation maximization (NPEM) algorithm. It computes the entire joint probability density for a 2 compartment absorptive model, even with mixed oral and intravenous input, and thus can obtain both Vd and bioavailability together. It makes no parametric assumptions such as mean, standard deviation, etc., but also gets them. It can thus discover unrecognized subpopulations. It reads routine patient data files from the clinical programs. Parameter values found can be entered and stored for use with the clinical programs.
3. The USC*PACK BOXES program makes customized PK/PD models by placing boxes on the screen and connecting them with arrows. Equations are automatically written for the Model part of the ADAPT I PC programs. Effect models (Hill or Keo) are easily made.

The programs run on the IBM PC and compatible machines. A math coprocessor is required. They need at least DOS 5.0, and 2.0 MB of memory (4 is better, and for NPEM2, the more there is, the faster it runs). The programs come on three 3.5 inch disks or on CD's.

Since Dec 2002, we must ask for an increased donation to offset our increasing costs. This applies even if you already have a previous USC*PACK program. However, upgrading from version 10.6 is free. These requested donations are:

                                        Hospital or          Commercial
                                   Academic Institution      or Industry
                                          $595.00              $895.00
 

Please print out, sign, and mail the enclosed license agreement back to us, with a check, made out to the University of Southern California. We will send the programs as soon as possible. If you have questions, write to us at 2250 Alcazar St., Los Angeles CA 90033, call us at (323) 442-1300, fax us at (323) 442-1302, or email us at jelliffe@usc.edu.