{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:40:09Z","timestamp":1790232009383,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"ViiV Healthcare and Janssen Research and Development"},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To characterize the population pharmacokinetics of the rilpivirine long-acting (LA) formulation after intramuscular administration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Rich and sparse rilpivirine plasma concentration data were obtained from seven clinical studies. In total, 18\u200a261 rilpivirine samples were collected from 986 subjects (131 healthy subjects from Phase I studies and 855 people living with HIV from Phase IIb\/III studies). Doses ranged from 300 to 1200\u2009mg, as single-dose or multiple-dose regimens (every 4 or 8\u2009weeks). In Phase III studies, an initiation injection of 900\u2009mg followed by continuation injections of 600\u2009mg every 4\u2009weeks was used. Non-linear mixed-effects modelling was performed using NONMEM\u00ae software.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A one-compartment model with linear elimination and two parallel absorption pathways (fast and slow) with sequential zero-first-order processes adequately captured rilpivirine flip-flop pharmacokinetics after intramuscular administration of the LA formulation. The estimated apparent elimination half-life of rilpivirine LA was 200\u2009days. None of the evaluated covariates (age, body weight, BMI, sex, race, health status and needle length) had a clinically relevant impact on rilpivirine pharmacokinetics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The population pharmacokinetic model suitably describes the time course and associated variability of rilpivirine plasma concentrations after rilpivirine LA intramuscular administration. The monthly regimen consists of an oral lead-in period (rilpivirine 25\u2009mg tablets once daily for 4\u2009weeks), followed by an initiation injection of 900\u2009mg rilpivirine LA, then 600\u2009mg rilpivirine LA continuation injections monthly. The absence of a clinically relevant effect of covariates on rilpivirine pharmacokinetics suggests that rilpivirine LA dose adjustments for specific subgroups are not warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab338","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T11:16:51Z","timestamp":1631099811000},"page":"3255-3262","source":"Crossref","is-referenced-by-count":27,"title":["Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV"],"prefix":"10.1093","volume":"76","author":[{"given":"M","family":"Neyens","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H M","family":"Crauwels","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"Perez-Ruixo","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Rossenu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, Janssen Research and Development, Beerse, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"2021111722581670600_dkab338-B1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3851\/IMP2084","article-title":"Beyond virological suppression: the role of adherence in the late HAART era","volume":"17","author":"Ammassari","year":"2012","journal-title":"Antivir 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