scholarly journals Fluoride Pharmacokinetics in Urine and Plasma Following Multiple Doses of MK‐8507, an Investigational, Oral, Once‐Weekly Non‐Nucleoside Reverse Transcriptase Inhibitor

2021 ◽  
Author(s):  
Gillian Gillespie ◽  
Deanne Jackson Rudd ◽  
Saijuan Zhang ◽  
Andrea Schaeffer ◽  
Charles Tomek ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Multiple Doses ◽  
Reverse Transcriptase Inhibitor

scholarly journals Pharmacokinetic and Safety Profile of the Novel HIV Non-Nucleoside Reverse Transcriptase Inhibitor MK-8507 in Adults without HIV

2021 ◽  
Author(s):  
Wendy Ankrom ◽  
Deanne Jackson Rudd ◽  
Andrea Schaeffer ◽  
Deborah Panebianco ◽  
Evan J. Friedman ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Oral Administration ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Viral Suppression ◽  
Transcriptase Inhibitor ◽  
Daily Administration ◽  
Multiple Doses ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

MK-8507 is a novel HIV-1 non-nucleoside reverse transcriptase inhibitor in clinical development with potential for once-weekly oral administration for the treatment of HIV-1 infection. Two randomized, double-blind, placebo-controlled phase 1 studies in adults without HIV-1 evaluated the safety, tolerability, and pharmacokinetics of single and multiple doses of MK-8507; drug interaction with midazolam (a cytochrome P450 3A4 substrate) and food effect were also assessed. In Study 1, 16 participants received oral ascending single doses of MK-8507 (2–400 mg) or placebo in an alternating fashion. In Study 2, 24 participants received ascending single doses of MK-8507 (400–1200 mg) or placebo and multiple doses (once weekly for 3 weeks) of MK-8507 (100–400 mg) or placebo. MK-8507 pharmacokinetics were approximately dose proportional at 2–1200 mg. MK-8507 had a time to maximum concentration of 2–7 hours and a mean terminal half-life of ∼58–84 hours. MK-8507 doses ≥100 mg achieved a plasma concentration at 168 hours post-dose (7 days) associated with antiviral efficacy. A high-fat meal had no clinically meaningful effect on MK-8507 pharmacokinetics, and MK-8507 400 mg once weekly had no clinically meaningful effect on midazolam pharmacokinetics. Single and multiple doses of MK-8507 were generally well tolerated. No trends with dose and no clinically meaningful changes were observed in vital signs, electrocardiograms, and laboratory safety tests. The pharmacokinetics and safety data are supportive of once-weekly oral administration and support further clinical investigation of MK-8507 for the treatment of HIV-1 infection. Over the last 3 decades, substantial improvements have been made in oral HIV antiretroviral therapies (ART), which now offer people living with HIV (PLWH) the potential for a near-normal life expectancy (1, 2). To achieve this, individuals must maintain life-long viral suppression, which requires daily administration of efficacious medication (3). Issues surrounding tolerability, complicated regimens, and treatment fatigue from daily dosing can lead to poor adherence and suboptimal viral suppression (3–6). Regimens can become complex when there is the need to take multiple pills, requirement to take a medication fasted or with food, or the potential for interactions with other medications, including those required to treat HIV-related comorbidities (3, 78). New treatment options that are not only highly effective but also offer excellent tolerability, a high barrier to resistance, favorable drug interaction profiles, and the potential for less frequent dosing remain the focus of much clinical research (7, 9). While 1 pill once a day meets the needs of many PLWH, for others daily administration poses challenges, including treatment fatigue and daily reminders and/or stigma associated with ART (10, 11). While treatment regimens that can be taken less often than daily are attractive to many PLWH, the long-acting injectable combination of cabotegravir/rilpivirine is currently the only treatment option available without daily dosing; however, administration requires injection by a health care professional (12), potentially posing other challenges.

Viral load outcome of non-nucleoside reverse transcriptase inhibitor regimens for 2203 mainly antiretroviral-experienced patients

AIDS ◽  
2001 ◽  
Vol 15 (18) ◽  
pp. 2385-2395 ◽  
Author(s):  
Andrew N. Phillips ◽  
Christian Pradier ◽  
Adriano Lazzarin ◽  
Bonaventura Clotet ◽  
Frank-Detlef Goebel ◽  
...  
Keyword(s):  
Viral Load ◽  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Reverse Transcriptase Inhibitor
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