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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000301
Original Article: PDF Only

GSK1265744 Pharmacokinetics in Plasma and Tissue Following Single-Dose Long-Acting (LA) Injectable Administration in Healthy Subjects.

Spreen, William PharmD; Ford, Susan L. PharmD; Chen, Shuguang PhD; Wilfret, David MD; Margolis, David MD; Gould, Elizabeth BS; Piscitelli, Stephen PharmD

Published Ahead-of-Print
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Background: GSK1265744 (744) is an HIV-1 integrase inhibitor (INI) in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics (PK) following single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous (SC) injections.

Methods: This was a Phase I, open-label, nine-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100 to 800 mg IM and 100 to 400 mg SC.

Results: Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in Cohorts 8 and 9, and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma PK sampling was performed for a minimum of 12 weeks or until 744 concentrations were <=0.1 [mu]g/mL. Rectal and cervicovaginal tissue biopsies were performed at Weeks 2 and 8 (Cohort 8) and Weeks 4 and 12 (Cohort 9). 744 LA was generally safe and well tolerated following single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks post dose. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16-weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations.

Conclusion: These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

(C) 2014 by Lippincott Williams & Wilkins


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