Universität zu Köln

Cawello, Willi, Fuhr, Uwe, Hering, Ursula, Maatouk, Haidar and Halabi, Atef (2013). Impact of Impaired Renal Function on the Pharmacokinetics of the Antiepileptic Drug Lacosamide. Clin. Pharmacokinet., 52 (10). S. 897 - 907. AUCKLAND: ADIS INT LTD. ISSN 1179-1926

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Abstract

Background and Objective The antiepileptic drug lacosamide is eliminated predominantly via the kidneys. Therefore, an evaluation of the impact of renal impairment on its pharmacokinetic profile is an important component of its safety assessment. The objective of this study was to evaluate the pharmacokinetic profile of lacosamide among individuals with renal impairment (mild, moderate, or severe) and among patients with end-stage renal disease (ESRD), including those on hemodialysis. Methods This was an open-label, Phase I trial. The pharmacokinetics of a single oral 100-mg lacosamide dose were evaluated in five groups of participants: healthy controls, patients with mild, moderate, or severe renal impairment, and patients with ESRD (with and without hemodialysis). Results Forty participants completed the trial, eight in each group. In healthy volunteers, renal clearance accounted for approximately 30 % of total body clearance [geometric mean 0.5897 l/h (coefficient of variation 37.9 %) vs 2.13 l/h (20.8 %)]. With severe renal impairment, renal clearance was approximately 11 % of total body clearance [0.1428 l/h (31.8 %) vs 1.34 l/h (26.9 %)]. Terminal half-life and systemic exposure were increased with renal impairment, while total body clearance, renal clearance, and urinary excretion were decreased. Strong positive correlations between creatinine clearance, renal clearance, and urinary excretion were observed. Among patients with ESRD, approximately 50 % of lacosamide was cleared from systemic circulation by 4-h hemodialysis. In patients with essentially no renal clearance, nonrenal clearance was still present (1.1 l/h). Lacosamide was well tolerated by healthy volunteers and patients. Conclusions In patients with mild-to-moderate renal impairment, lacosamide dose adjustment is not necessary, because total body clearance decreased by only approximately 20 %. Dose adjustment, however, is required for patients with severe renal impairment. Hemodialysis removes approximately 50 % of lacosamide from plasma; therefore, dose supplementation following hemodialysis should be considered.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cawello, Willi UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Hering, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Maatouk, Haidar UNSPECIFIED UNSPECIFIED UNSPECIFIED Halabi, Atef UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-474652
DOI:	10.1007/s40262-013-0080-7
Journal or Publication Title:	Clin. Pharmacokinet.
Volume:	52
Number:	10
Page Range:	S. 897 - 907
Date:	2013
Publisher:	ADIS INT LTD
Place of Publication:	AUCKLAND
ISSN:	1179-1926
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PARTIAL-ONSET SEIZURES; RANDOMIZED CONTROLLED-TRIAL; HEALTHY-VOLUNTEERS; ADJUNCTIVE THERAPY; EFFICACY; SAFETY Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47465