Pharmacokinetic, Safety, and Antiviral Profiles of Oral Ganciclovir in Persons Infected with Human Immunodeficiency Virus: A Phase I/II Study

• Published in: The Journal of infectious diseases Vol. 171; no. 6; pp. 1431 - 1437
• Main Authors: Spector, Stephen A., Busch, David F., Follansbee, Stephen, Squires, Kathryn, Lalezari, Jacob P., Jacobson, Mark A., Connor, James D., Jung, Donald, Shadman, Anna, Mastre, Barbara, Buhles, William, Drew, W. Lawrence
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.06.1995; University of Chicago Press
• Subjects: AIDS; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antivirals; Biological and medical sciences; Cultural groups; Cytomegalovirus; Cytomegalovirus infections; Dosage; Health care administration; human immunodeficiency virus; Major Articles; Medical sciences; Pharmacokinetics; Pharmacology. Drug treatments; Preventive medicine; Retinitis; Human; Immunopathology; Acyclic nucleoside; Purine nucleoside; Toxicity; Treatment efficiency; Oral administration; AIDS; Immune deficiency; Infection; Chemotherapy; Treatment; Viral disease; Phase II trial; Antiviral; Pharmacokinetics
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/171.6.1431

A phase I/II study evaluated the pharmacokinetics, tolerability, and antiviral activity of oral ganciclovir in persons infected with human immunodeficiency 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 µg/mL, and mean trough level was 0.54 µg/mL. The time to maximum serum drug concentration was 1.0–2.9 h, with a serum half-life of 3.0–7.3 h, suggesting prolonged oral absorption. Serious adverse events were uncommon. Decreased cytomegalovirus (CMV) shedding was observed from all sites. The median days (by dosage) to retinitis progression assessed by retinal examination after initiation of oral ganciclovir 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 profiles that may prove beneficial for both maintenance therapy of CMV retinitis and prevention of CMV disease in HIV-infected persons.