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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...

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Autores principales: Smith, William B, Mannaert, Erik, Verhaeghe, Tom, Kerstens, René, Vandeplassche, Lieve, Van de Velde, Vera
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
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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.
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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
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