{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:26:42Z","timestamp":1762608402727},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>MK\u20108507 is an investigational HIV\u20101 nonnucleoside reverse transcriptase inhibitor being developed for the treatment of HIV\u20101 infection. MK\u20108507 contains 2 trifluoromethyl groups that may result in fluoride release through metabolism, but the extent of MK\u20108507\u2013related fluoride release in humans has yet to be determined. This double\u2010blind, placebo\u2010controlled, 2\u2010period, parallel\u2010group, multiple\u2010dose trial in healthy participants without HIV\u20101 who were administered a fluoride\u2010restricted diet and once\u2010weekly doses of MK\u20108507 aimed to estimate the relationship between MK\u20108507 dose and fluoride exposure. A total of 15 adult male and 3 adult female (of non\u2010childbearing potential) participants were randomized to receive MK\u20108507 200 mg (n = 6), MK\u20108507 800 mg (n = 6), or placebo (n = 6). Change from baseline in mean daily fluoride excretion averaged over 7 days following the administration of MK\u20108507 200 mg resulted in a net mean increase of 19.8 \u03bcmol (90% confidence interval, 12.2\u201027.4) relative to placebo and did not exceed 57 \u03bcmol, a threshold related to the mean difference between the daily reference dose set by the US Environmental Protection Agency and the average dietary fluoride intake in the United States. However, daily urinary fluoride excretion exceeded the threshold following administration of 800 mg MK\u20108507 (75.1 \u03bcmol [90% confidence interval, 67.5\u201082.7]). Assuming a linear relationship between MK\u20108507 dose and estimated mean daily fluoride released at steady\u2010state, data interpolation suggests that the US Environmental Protection Agency reference dose for fluoride would not be exceeded in most patients when administering MK\u20108507 at doses currently under clinical investigation (\u2264400 mg once weekly).<\/jats:p>","DOI":"10.1002\/jcph.1957","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T05:03:38Z","timestamp":1629954218000},"page":"199-205","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fluoride Pharmacokinetics in Urine and Plasma Following Multiple Doses of MK\u20108507, an Investigational, Oral, Once\u2010Weekly Nonnucleoside Reverse Transcriptase Inhibitor"],"prefix":"10.1002","volume":"62","author":[{"given":"Gillian","family":"Gillespie","sequence":"first","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanne","family":"Jackson Rudd","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Tomek","sequence":"additional","affiliation":[{"name":"Celerion  Lincoln Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Larson","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"AnkromW SchurmannD Jackson RuddD et\u00a0al.Single doses of MK\u20108507 a novel HIV\u20101 NNRTI reduced HIV viral load for at least a week. Oral O416. Presented at: HIV Glasgow; October 5\u20138 2020(virtual event)."},{"key":"e_1_2_9_3_1","unstructured":"AnkromW SchaefferA PanebiancoD et\u00a0al.Safety tolerability and pharmacokinetics following single\u2010 and multiple\u2010dose administration of the novel NNRTI MK\u20108507 with a midazolam interaction arm. Poster presented at: HIV Glasgow; October 5\u20138 2020(virtual event). 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