Population pharmacokinetics of riociguat and its metabolite in patients with chronic thromboembolic pulmonary hypertension from routine clinical practice.
NONMEM
creatinine clearance
desmethylriociguat
total bilirubin
Journal
Pulmonary circulation
ISSN: 2045-8932
Titre abrégé: Pulm Circ
Pays: United States
ID NLM: 101557243
Informations de publication
Date de publication:
Historique:
received:
21
10
2019
accepted:
09
12
2019
entrez:
26
2
2020
pubmed:
26
2
2020
medline:
26
2
2020
Statut:
epublish
Résumé
Pharmacokinetic data for riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have previously been reported from randomized clinical trials, which may not fully reflect the population encountered in routine practice. The aim of the current study was to characterize the pharmacokinetic of riociguat and its metabolite M1 in the patients from routine clinical practice. A population pharmacokinetic model was developed in NONMEM 7.3, based on riociguat and its metabolite plasma concentrations from 49 patients with CTEPH. One sample with riociguat and M1 concentrations was available from each patient obtained at different time points after last dose. Age, bodyweight, sex, smoking status, concomitant medications, kidney and liver function markers were tested as potential covariates of pharmacokinetic of riociguat and its metabolite. Riociguat and M1 disposition was best described with one-compartment models. Apparent volume of distribution (Vd/F) for riociguat and M1 were assumed to be the same. Total bilirubin and creatinine clearance were the most predictive covariates for apparent riociguat metabolic clearance to M1 (CL
Identifiants
pubmed: 32095231
doi: 10.1177/2045894019898031
pii: 10.1177_2045894019898031
pmc: PMC7011339
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2045894019898031Informations de copyright
© The Author(s) 2020.
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