Conte JE, Lee B, Delahunty T, Lin E, Zurlinden E, Duncan S, McKenna E, Golden JA; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18; 10 (abstract no. A49).

University of California, San Francisco, CA.

53 (age 35 plus or minus 8 yrs; 30 men, 23 women; 16 HIV+, 37 HIV-, 25 slow acetylators, 28 fast acetylators) of 80 volunteer subjects without tuberculosis have been enrolled in a study of the IP of orally administered INH at steady state. The study is designed (8 subgroups of 10 subjects each) to measure the effect of gender, HIV status and acetylator status on peak (C(peak)) and 4 hour (C(4hr)) plasma concentrations, and drug concentrations in epithelial lining fluid (ELF) and alveolar cells (AC). The effects of gender and HIV status on drug concentrations in these compartments will be assessed using analysis of variance (ANOVA) and a three factor design. Standardized bronchoscopy and bronchoalveolar lavage (BAL) is performed at 4 hours post drug administration. Drug concentrations (mean plus or minus SD) have been measured using sensitive (10 ng/ml in BAL and AC, and 100 ng/ml in plasma) and specific high pressure column chromatography (HPLC). Because enrollment into the sub-groups has not yet been completed, a preliminary descriptive analysis of the data is presented. The mean (plus or minus SD) C(peak) and C(4hr) were 2.1 plus or minus 1.8 mcg/ml and 0.8 plus or minus 0.8 mcg/ml (n=52), respectively. However 12 subjects had both C(peak) and C(4hr) measurements of less than 1 mcg/ml. The mean (plus or minus SD) concentration of INH in AC was 8.0 plus or minus 8.5 mcg/ml (n=15). In 3 subjects INH was undetectable in AC. The mean (plus or minus SD) concentration in ELF was 2.6 plus or minus 4.1 mcg/ml (n=52). In 14 subjects INH was undetectable in ELF. These preliminary data suggest that a wide range of INH concentrations is present in plasma, ELF and AC and that sub-therapeutic concentrations are present in these compartments in many of these subjects.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Bronchoscopy
• Drug Administration Routes
• Female
• HIV Infections
• HIV Seropositivity
• Humans
• Immunoprecipitation
• Isoniazid
• Male
• pharmacokinetics

Other ID:

• 98927581

UI: 102234755

From Meeting Abstracts