Wynn H, Shelton MJ, Bartos L, DiFrancesco R, Hewitt RG; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 24 (abstract no. 660).

SUNY Buffalo, Buffalo, NY

BACKGROUND: GJ inhibits metabolism of certain drugs metabolized by cytochrome P4503A4. Although IDV is a substrate for P4503A4, GJ reduced exposure to single IDV doses by 26% in volunteers. IDV absorption may depend upon gastric acid, but the effects of GJ on gastric pH are unreported.METHODS: To determine the effect of GJ on IDV exposure and gastric pH, 15 HIV+ patients receiving indinavir, but no other medications suspected to affect P450 3A4, participated in a steady-state, IDV pharmacokinetic study. 14 patients had normal gastric acid (minimum gastric pH < 3) and 1 patient had spontaneous gastric hypoacidity (GH, pH >/= 3). All patients were studied randomly in a fasting state: IDV given with water (H2O) versus IDV given with double-strength GJ (6 ounces of each). Plasma samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, and 5 hours after dosing and assayed using a high performance liquid chromatography method. Gastric pH was monitored with radiotelemetry and reported as median values within 30 minutes of IDV dosing. IDV pharmacokinetic (PK) parameters were determined using noncompartmental methods. PK parameters and pH values were log-transformed and compared using repeated measures analysis of variance.RESULTS: Median +/- standard deviation for patients with normal gastric acid: [table: see text] GJ increased gastric pH, but was not associated with differences in IDV pharmacokinetics, despite 90% power to detect a 30% difference. The patient with GH had IDV parameters similar to those with normal gastric acid.CONCLUSIONS: Double-strength GJ increases gastric pH of patients without GH, but has little, if any, effect upon exposure to IDV.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Beverages
• HIV Infections
• HIV Seropositivity
• Humans
• Indinavir
• injuries

Other ID:

• GWAIDS0007143

UI: 102244639

From Meeting Abstracts