Cox SR, Phillips L, Grasela TH; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 321 (abstract no. Tu.B.2324).
Pharmacia and Upjohn, Inc., Kalamazoo, MI. Fax: 616 385-7435.
Objective: To develop a PPK model which can be used to analyze DLV concentration (conc) data from Phase III studies. Methods: Plasma DLV conc data were pooled from 7 multiple-dose PK studies which included total daily DLV doses of 60-1200 mg and extensive sampling for DLV conc after at least two doses. The database contained 3996 conc records from 128 patients, and DLV conc ranged from 0.06-100 micromolars (median 8 micromolars). Modeling was performed with NONMEM. Results: Single and multiple-dose PK of DLV were best described by a 1-compartment model with 1st-order absorption, parallel 1st-order and Michaelis-Menten clearance, and a nonlinear bioavailability function. To account for a DLV-induced inhibition of metabolism, Vm was allowed to change after 24 hr. Residual and inter-individual variability were described by proportional error and combination additive+proportional error models, respectively. The median prediction errors (predicted-measured conc) were 0.6 micromolars and -0.9 micromolars for measured conc of 0-5 micromolars and greater than 5 micromolars, respectively. Residual variability was less than 32% CV. Conclusion: This PPK model adequately describes the pooled DLV data and will be further evaluated in analyses of Phase III data. (table: see text)
Publication Types:
Keywords:
- Delavirdine
- HIV-1
- Humans
- Models, Biological
- metabolism
- pharmacokinetics
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102218425
From Meeting Abstracts