Cargando…
Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study
OBJECTIVE: To evaluate the pharmacokinetics of prucalopride in individuals with renal impairment (RI). METHODS: This open-label Phase I study (ClinicalTrials.gov identifier: NCT01674192) enrolled men and women aged 18–75 years who were classified by renal function: normal renal function (creatinine...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529624/ https://www.ncbi.nlm.nih.gov/pubmed/23269861 http://dx.doi.org/10.2147/DDDT.S36142 |
_version_ | 1782253937054711808 |
---|---|
author | Smith, William B Mannaert, Erik Verhaeghe, Tom Kerstens, René Vandeplassche, Lieve Van de Velde, Vera |
author_facet | Smith, William B Mannaert, Erik Verhaeghe, Tom Kerstens, René Vandeplassche, Lieve Van de Velde, Vera |
author_sort | Smith, William B |
collection | PubMed |
description | OBJECTIVE: To evaluate the pharmacokinetics of prucalopride in individuals with renal impairment (RI). METHODS: This open-label Phase I study (ClinicalTrials.gov identifier: NCT01674192) enrolled men and women aged 18–75 years who were classified by renal function: normal renal function (creatinine clearance ≥ 80 mL/min/1.73 m(2)), mild RI (50–79 mL/min/1.73 m(2)), moderate RI (25–49 mL/min/1.73 m(2)), and severe RI (≤24 mL/min/1.73 m(2)). All received a single oral dose of prucalopride 2 mg. RESULTS: Thirty-four individuals (normal renal function: 10; mild RI: 8; moderate RI: 7; severe RI: 9) received prucalopride. In all groups, maximum plasma concentration was reached within 2–4 hours. There was no significant difference in exposure (area under the plasma concentration–time curve from time zero to infinity) between participants with mild RI and those with normal renal function. However, area under the plasma concentration–time curve from time zero to infinity values were 1.5- and 2.3-fold higher (P = 0.002 and P < 0.001) in patients with moderate RI and severe RI, respectively, than in those with normal renal function. The proportion of total body clearance accounted for by renal clearance was significantly reduced in those with RI. CONCLUSION: Clinically meaningful reductions in renal clearance were seen in participants with severe RI, which supports a decrease from the standard dose of prucalopride 2 mg daily to 1 mg daily in these individuals. |
format | Online Article Text |
id | pubmed-3529624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35296242012-12-26 Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study Smith, William B Mannaert, Erik Verhaeghe, Tom Kerstens, René Vandeplassche, Lieve Van de Velde, Vera Drug Des Devel Ther Original Research OBJECTIVE: To evaluate the pharmacokinetics of prucalopride in individuals with renal impairment (RI). METHODS: This open-label Phase I study (ClinicalTrials.gov identifier: NCT01674192) enrolled men and women aged 18–75 years who were classified by renal function: normal renal function (creatinine clearance ≥ 80 mL/min/1.73 m(2)), mild RI (50–79 mL/min/1.73 m(2)), moderate RI (25–49 mL/min/1.73 m(2)), and severe RI (≤24 mL/min/1.73 m(2)). All received a single oral dose of prucalopride 2 mg. RESULTS: Thirty-four individuals (normal renal function: 10; mild RI: 8; moderate RI: 7; severe RI: 9) received prucalopride. In all groups, maximum plasma concentration was reached within 2–4 hours. There was no significant difference in exposure (area under the plasma concentration–time curve from time zero to infinity) between participants with mild RI and those with normal renal function. However, area under the plasma concentration–time curve from time zero to infinity values were 1.5- and 2.3-fold higher (P = 0.002 and P < 0.001) in patients with moderate RI and severe RI, respectively, than in those with normal renal function. The proportion of total body clearance accounted for by renal clearance was significantly reduced in those with RI. CONCLUSION: Clinically meaningful reductions in renal clearance were seen in participants with severe RI, which supports a decrease from the standard dose of prucalopride 2 mg daily to 1 mg daily in these individuals. Dove Medical Press 2012-12-18 /pmc/articles/PMC3529624/ /pubmed/23269861 http://dx.doi.org/10.2147/DDDT.S36142 Text en © 2012 Smith et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Smith, William B Mannaert, Erik Verhaeghe, Tom Kerstens, René Vandeplassche, Lieve Van de Velde, Vera Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study |
title | Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study |
title_full | Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study |
title_fullStr | Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study |
title_full_unstemmed | Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study |
title_short | Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study |
title_sort | effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label phase i study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529624/ https://www.ncbi.nlm.nih.gov/pubmed/23269861 http://dx.doi.org/10.2147/DDDT.S36142 |
work_keys_str_mv | AT smithwilliamb effectofrenalimpairmentonthepharmacokineticsofprucaloprideasingledoseopenlabelphaseistudy AT mannaerterik effectofrenalimpairmentonthepharmacokineticsofprucaloprideasingledoseopenlabelphaseistudy AT verhaeghetom effectofrenalimpairmentonthepharmacokineticsofprucaloprideasingledoseopenlabelphaseistudy AT kerstensrene effectofrenalimpairmentonthepharmacokineticsofprucaloprideasingledoseopenlabelphaseistudy AT vandeplasschelieve effectofrenalimpairmentonthepharmacokineticsofprucaloprideasingledoseopenlabelphaseistudy AT vandeveldevera effectofrenalimpairmentonthepharmacokineticsofprucaloprideasingledoseopenlabelphaseistudy |