Our current work has involved development of a pharmacokinetic model for the drug delavirdien (DLV), a recently-approved reverse transcriptase inhibitor, used in combination regimens to treat AIDS. During development, the drug was dosed, in several trials, using adaptive feedback control of 'trough' plasma concentrations. A typical starting regimen is 876.1 (moles (400 mg), given orally, every 8 hours. Both parent DLV (also called U90) and metabolite (N-DLV or U96) concentrations were assayed as feedback. The kinetic model has bolus inputs into an absorptive site, then first order absorption (ka) after a lag time. DLV distributes into central and peripheral compartments with rate of equilibration governed by Cld (Cld = Vc(kcp = Vp(kpc). DLV is eliminated, from the central compartment, by parallel capacity-limited (saturable) and first order clearance pathways (CL90). We parameterize the saturable pathway by Km and intrinsic clearance (CLi = Vmax/Km). DLV which is cleared by the saturable pathway is metabolized to N-DLV, which we modeled as distributing into a single compartment from which drug is cleared by a first order process (CL96). This model is currently being used to analyze data from 40 patients as part of a Phase 2 clinical trial of DLV in HIV infected patients.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001861-17
Application #
6480880
Study Section
Project Start
2001-09-01
Project End
2002-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
17
Fiscal Year
2001
Total Cost
$155,764
Indirect Cost
Name
University of Southern California
Department
Type
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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