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      Effect of renal impairment on the pharmacokinetics of prucalopride: a single- dose open-label Phase I study

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          Abstract

          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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          Author and article information

          Journal
          Drug Des Devel Ther
          Drug Des Devel Ther
          Drug Design, Development and Therapy
          Dove Medical Press
          1177-8881
          2012
          18 December 2012
          : 6
          : 407-415
          Affiliations
          [1 ]Volunteer Research Group and New Orleans Center for Clinical Research, The University of Tennessee Medical Center, Knoxville, TN, USA
          [2 ]Janssen Research and Development, a division of Janssen Pharmaceutica NV, Beerse, Belgium
          [3 ]Shire-Movetis NV, Turnhout, Belgium
          [4 ]Independent Consultant Clinical Pharmacokinetics, Princeton, NJ, USA
          Author notes
          Correspondence: Lieve Vandeplassche, Shire-Movetis NV, Veedijk 58 (1004), 2300 Turnhout, Belgium, Tel +32 14 404 355, Email lvandeplassche@ 123456shire.com
          Article
          dddt-6-407
          10.2147/DDDT.S36142
          3529624
          23269861
          © 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.

          Categories
          Original Research

          Pharmacology & Pharmaceutical medicine

          safety, prucalopride, pharmacokinetics, renal impairment

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