Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers

• Published in: Journal of antimicrobial chemotherapy Vol. 66; no. 7; pp. 1567 - 1572
• Main Authors: Patel, Parul, Song, Ivy, Borland, Julie, Patel, Apurva, Lou, Yu, Chen, Shuguang, Wajima, Toshihiro, Peppercorn, Amanda, Min, Sherene S., Piscitelli, Stephen C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2011; Oxford Publishing Limited (England)
• Subjects: Acids; Adult; Antacids - administration & dosage; Anthracenes - adverse effects; Anthracenes - pharmacokinetics; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chemotherapy; Female; Healthy Volunteers; Heterocyclic Compounds, 3-Ring; HIV; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Kinetics; Male; Medical sciences; Pharmacology. Drug treatments; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Vitamins; Vitamins - administration & dosage; metal cations; drug interaction; antiretroviral therapy; Human; Immunopathology; Antiretroviral agent; Healthy subject; AIDS; Metal; Reducing agent; Immune deficiency; Infection; Chemotherapy; Integrase inhibitor; Multivitamin; Treatment; Viral disease; Antiviral; Cations; Drug interaction; Pharmacokinetics
• DOI: 10.1093/jac/dkr139
• ISSN: 0305-7453; 1460-2091

Objectives To evaluate the effect of pH-altering agents on S/GSK1349572 exposure in healthy subjects. Methods S/GSK1349572 is an unboosted, once-daily, next-generation HIV integrase inhibitor. In the first study, 16 subjects received four single-dose treatments: (i) S/GSK1349572 50 mg; (ii) S/GSK1349572 50 mg with a multivitamin (MVI; One A Day Maximum); (iii) S/GSK1349572 50 mg with a liquid antacid (Maalox Advanced Maximum Strength); and (iv) S/GSK1349572 50 mg 2 h before an antacid. In the second study, 12 subjects received a single dose of S/GSK1349572 alone and on day 5 of omeprazole. Results All treatments were well tolerated. MVI co-administration modestly decreased S/GSK1349572 AUC by 33%. Concurrent antacid co-administration reduced S/GSK1349572 AUC by 74% and staggered antacid dosing significantly diminished this interaction, with a reduction in S/GSK1349572 AUC of 26%. Omeprazole did not significantly affect S/GSK1349572 exposure. Conclusions S/GSK1349572 can be taken with proton pump inhibitors and MVIs without dose adjustment but should be administered 2 h before or 6 h after antacids.