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

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 m²), mild RI (50–79 mL/min/1.73 m²), moderate RI (25–49 mL/min/1.73 m²), and severe RI (≤24 mL/min/1.73 m²). 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.

Keywords:

• renal impairment
• pharmacokinetics
• prucalopride
• safety

Acknowledgments

Clinical research was funded by the sponsors, Janssen Pharmaceutica NV and Shire-Movetis NV. Under the direction of the authors, Catherine Hill, PhD, an employee of PharmaGenesis™ London, provided writing assistance for this publication. Editorial assistance in formatting, proofreading, copy editing, and fact checking was provided by Oxford PharmaGenesis™ Ltd. Slavka Baronikova PhD from Shire-Movetis NV also reviewed and edited the manuscript for scientific accuracy. Shire-Movetis NV provided funding to Oxford PharmaGenesis™ Ltd, for support in writing and editing this manuscript. Although the sponsor was involved in the design, collection, analysis, interpretation, and fact checking of information, the content of this manuscript, the ultimate interpretation, and the decision to submit it for publication in Drug Design, Development and Therapy was made by the authors independently. Resolor is a CTM registered trademark of Shire-Movetis NV.

Disclosure

EM and TV are employees of Janssen Research and Development, Janssen Pharmaceutica NV in Belgium. RK and LV are employees of Shire-Movetis NV in Belgium and own stocks in Shire. VV is a consultant for Shire-Movetis. WBS received a grant to the New Orleans Center for Clinical Research for participation in this study.