Awardee OrganizationUNIVERSITY OF SOUTHERN CALIFORNIA
Description
Abstract Text
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.
No Sub Projects information available for 5P41RR001861-18 0011
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