PHARMACOKINETIC, SAFETY, AND ANTIVIRAL PROFILES OF ORAL GANCICLOVIR IN PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS - A PHASE I II STUDY/

A phase I/II study evaluated the pharmacokinetics, tolerability, and a ntiviral activity of oral ganciclovir in persons infected with human i mmunodeficiency virus (HIV). Oral bioavailability ranged from 2.6% to 7.3%. The mean maximum serum concentration achieved at 1000 mg every 8 h was 1.11 mu g/mL, and mean trough level was 0.54 mu g/mL. The time to maximum serum drug concentration was 1.0-2.9 h, with a serum half-l ife of 3.0-7.3 h, suggesting prolonged oral absorption. Serious advers e events were uncommon. Decreased cytomegalovirus (CMV) shedding was o bserved from all sites. The median days (by dosage) to retinitis progr ession assessed by retinal examination after initiation of oral gancic lovir were 62 (1000 mg every 8 h), 148 (500 mg every 3 h), 75 (750 mg every 3 h), 148 (1000 mg every 3 h), and 139 (2000 mg every 8 h). Thus , oral ganciclovir has pharmacokinetic, toxicity, and antiviral profil es that may prove beneficial for both maintenance therapy of CMV retin itis and prevention of CMV disease in HIV-infected persons.