Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV.
Objectives: To characterize the population pharmacokinetics of the rilpivirine long-acting (LA) formulation after intramuscular administration.Methods: Rich and sparse rilpivirine plasma concentration data were obtained from seven clinical studies. In total, 18 261 rilpivirine samples were collected...
| Publicado en: | Journal of Antimicrobial Chemotherapy (JAC) Vol. 76; no. 12; pp. 3255 - 3263 |
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| Autores principales: | , , , |
| Formato: | research Journal Article |
| Publicado: |
Oxford University Press / USA
Dec2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=153738442&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 153738442 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03057453 N5O jtl: Journal of Antimicrobial Chemotherapy (JAC) issn: 03057453 maglogo: N pubinfo: dt: Dec2021 vid: 76 iid: 12 pid: 622 pub: Oxford University Press / USA artinfo: ui: 153738442 153738442 NLM34510179 153738442 10.1093/jac/dkab338 NLM34510179 153738442 ppf: 3255 ppct: 8 formats: tig: atl: Population pharmacokinetics of the rilpivirine long-acting formulation after intramuscular dosing in healthy subjects and people living with HIV. aug: au: Neyens, M Crauwels, H M Perez-Ruixo, J J Rossenu, S affil: Clinical Pharmacology and Pharmacometrics, Janssen Research and Development , Beerse, Belgium sug: subj: HIV Infections Drug Therapy Anti-HIV Agents Therapeutic Use Injections, Intramuscular Human Research Subjects Comparative Studies Multicenter Studies Evaluation Research Validation Studies Clinical Assessment Tools Impact of Events Scale Funding Source ab: Objectives: To characterize the population pharmacokinetics of the rilpivirine long-acting (LA) formulation after intramuscular administration.Methods: Rich and sparse rilpivirine plasma concentration data were obtained from seven clinical studies. In total, 18 261 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 mg, as single-dose or multiple-dose regimens (every 4 or 8 weeks). In Phase III studies, an initiation injection of 900 mg followed by continuation injections of 600 mg every 4 weeks was used. Non-linear mixed-effects modelling was performed using NONMEM® software.Results: 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 days. None of the evaluated covariates (age, body weight, BMI, sex, race, health status and needle length) had a clinically relevant impact on rilpivirine pharmacokinetics.Conclusions: 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 mg tablets once daily for 4 weeks), followed by an initiation injection of 900 mg rilpivirine LA, then 600 mg 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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