Pharmacokinetics of emedastine difumarate, a new anti-histaminic agent in patients with renal impairment.
OBJECTIVE
Emedastine difumarate is a new H1 receptor antagonist with well defined pharmacokinetic and pharmacodynamic profiles in healthy volunteers. However, to date it is not known whether impaired renal function in patients with chronic renal insufficiency affects its pharmacokinetics and probably also its tolerability. Therefore, we here set out to compare the pharmacokinetics of emedastine difumarate in patients suffering from different degrees of renal failure with a control group of healthy volunteers.


RESULTS
For this purpose we conducted an open, single-centre, comparative parallel group study in patients and healthy volunteers. Emedastine difumarate 2 mg was administered orally to the study population in single and seven repetitive doses twice daily (b.i.d.). Pharmacokinetics differed markedly between volunteers (n = 6) and patients (n = 17). The maximum serum concentration of emedastine (Cmax), area under the serum concentration-time curve, mean residence time and terminal disposition half-life were significantly higher in patients (P < 0.05), while time to reach Cmax and apparent volume of disposition were not statistically different after single and repeated (steady-state) oral administrations. Blood pressure and heart rate were also not affected by the study medication.


CONCLUSIONS
The present study shows that impaired renal function alters the pharmacokinetics of emedastine in plasma. Thus, dose adjustment of emedastine difumarate is advisable in patients with impaired renal function.
Joukhadar
C
C
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Allgemeines Krankenhaus, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Herranz
U
U
Pernerstorfer
T
T
Assandri
A
A
Klein
N
N
Schrolnberger
C
C
Lackner
E
E
Eichler
H G
HG
Müller
M
M
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; C043345:emedastine