Shelton M, Adams J, Grasela T, Hewitt R, DeRemer M, Morse G; National Conference on Human Retroviruses and Related Infections.
Program Abstr First Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 1st 1993 Wash DC. 1993 Dec 12-16; 134.
State University of New York at Buffalo, Buffalo, NY.
Didanosine (ddI) is approved as second-line therapy of HIV infection. We sought to characterize ddI pharmacokinetics (PPK) in our HIV outpatient population. 52 patients (96 percent male, 73 percent Caucasian) with various risk factors for HIV acquisition (30 percent gay, 20 percent IVDU) have been evaluated to date. During each clinic visit, questionnaires were completed by patients to determine ddI dosing histories, and timed plasma samples were collected whenever blood samples were ordered for routine patient care. ddI was measured by radioimmunoassay, and PPK estimates were derived via NONMEM. Preliminary results from patients receiving ddI monotherapy (n=50) or ddI/ZDV combination therapy (n=2) for 183 +/- 158 days are available. At initiation of ddI therapy, mean patient age and serum creatinine were 40 +/- 8.8 years and 0-94 +/- 0.2 mg/dl, respectively, ddI regimens ranged from 50 mg q 24h to 200 mg q 12h (as tablet formulation or equivalent) 107 plasma samples were collected at a mean of 3.8 +/- 2.2 h after dosing (range 1-11.75h). ddI was detectable in most samples collected less than 12h after dosing. Using a one compartment PPK model, mean (CV) CI/F = 190 (9 percent) L/h and Vd/F = 400 (14 percent) L. Interindividual variability in CI/F was 23 percent. Using weight-adjusted PPK parameters did not improve model fit or precision of estimates. Assuming F = 30 percent CI/F estimates agree with values obtained from traditional pharmacokinetic studies, but our Vd/F estimate is twofold higher. Thus sparse sampling strategies may provide reasonable population estimates of C/F for ddI in this population.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Didanosine
- HIV Infections
- HIV Seropositivity
- Humans
- Male
- Zidovudine
- pharmacokinetics
Other ID:
UI: 102214400
From Meeting Abstracts