Pharmacokinetics and safety of ebastine in healthy subjects and patients with renal impairment

Robert J. Noveck, Richard A Preston, Suzanne K. Swan

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: To assess the differences in the pharmacokinetics and cardiac safety of ebastine and its active metabolite, carebastine, in patients with normal and impaired renal function. Methods: Twenty-four patients with varying degrees of renal impairment (mild, moderate or severe: n = 8 per group) and 12 healthy subjects participated in an open-label, parallel-group, multicentre study. Ebastine 20mg was administered orally once daily for 5 days. Plasma concentrations of ebastine and carebastine were determined for 24 hours on day 1 and for 72 hours on day 5 by using a validated sensitive liquid chromatography-tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 ng/mL for ebastine and 1.00 ng/mL for carebastine. Renal function was assessed by measuring 24-hour creatinine clearance (CLCR) at baseline. Cardiac and general safety parameters were also monitored. Results: The pharmacokinetics of ebastine were not modified by renal impairment. No correlation between ebastine pharmacokinetics and renal function, as expressed by CLCR assessed 2 days prior to dosing, was observed. Comparison of the plasma exposure and the elimination half-life of ebastine and carebastine between groups showed no significant differences. Therefore, no apparent accumulation of ebastine and carebastine occurred, and steady-state concentrations of ebastine and carebastine were predictable from single-dose pharmacokinetics for both healthy subjects and patients with renal impairment, even though the variability between the groups was large. In addition, no differences were observed in the safety of ebastine between patients with renal impairment and healthy subjects when assessing adverse events, vital signs, laboratory parameters or ECGs. Conclusion: Ebastine was generally well tolerated in subjects with impaired renal function. No clinically important pharmacokinetic or safety differences were observed between patients with renal impairment and healthy subjects with normal renal function.

Original languageEnglish
Pages (from-to)525-534
Number of pages10
JournalClinical Pharmacokinetics
Volume46
Issue number6
DOIs
StatePublished - Jun 1 2007

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Healthy Volunteers
Pharmacokinetics
Kidney
Safety
ebastine
Vital Signs
Tandem Mass Spectrometry
Liquid Chromatography
Multicenter Studies
Half-Life
carebastine
Creatinine
Electrocardiography

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Pharmacokinetics and safety of ebastine in healthy subjects and patients with renal impairment. / Noveck, Robert J.; Preston, Richard A; Swan, Suzanne K.

In: Clinical Pharmacokinetics, Vol. 46, No. 6, 01.06.2007, p. 525-534.

Research output: Contribution to journalArticle

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abstract = "Objective: To assess the differences in the pharmacokinetics and cardiac safety of ebastine and its active metabolite, carebastine, in patients with normal and impaired renal function. Methods: Twenty-four patients with varying degrees of renal impairment (mild, moderate or severe: n = 8 per group) and 12 healthy subjects participated in an open-label, parallel-group, multicentre study. Ebastine 20mg was administered orally once daily for 5 days. Plasma concentrations of ebastine and carebastine were determined for 24 hours on day 1 and for 72 hours on day 5 by using a validated sensitive liquid chromatography-tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 ng/mL for ebastine and 1.00 ng/mL for carebastine. Renal function was assessed by measuring 24-hour creatinine clearance (CLCR) at baseline. Cardiac and general safety parameters were also monitored. Results: The pharmacokinetics of ebastine were not modified by renal impairment. No correlation between ebastine pharmacokinetics and renal function, as expressed by CLCR assessed 2 days prior to dosing, was observed. Comparison of the plasma exposure and the elimination half-life of ebastine and carebastine between groups showed no significant differences. Therefore, no apparent accumulation of ebastine and carebastine occurred, and steady-state concentrations of ebastine and carebastine were predictable from single-dose pharmacokinetics for both healthy subjects and patients with renal impairment, even though the variability between the groups was large. In addition, no differences were observed in the safety of ebastine between patients with renal impairment and healthy subjects when assessing adverse events, vital signs, laboratory parameters or ECGs. Conclusion: Ebastine was generally well tolerated in subjects with impaired renal function. No clinically important pharmacokinetic or safety differences were observed between patients with renal impairment and healthy subjects with normal renal function.",
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N2 - Objective: To assess the differences in the pharmacokinetics and cardiac safety of ebastine and its active metabolite, carebastine, in patients with normal and impaired renal function. Methods: Twenty-four patients with varying degrees of renal impairment (mild, moderate or severe: n = 8 per group) and 12 healthy subjects participated in an open-label, parallel-group, multicentre study. Ebastine 20mg was administered orally once daily for 5 days. Plasma concentrations of ebastine and carebastine were determined for 24 hours on day 1 and for 72 hours on day 5 by using a validated sensitive liquid chromatography-tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 ng/mL for ebastine and 1.00 ng/mL for carebastine. Renal function was assessed by measuring 24-hour creatinine clearance (CLCR) at baseline. Cardiac and general safety parameters were also monitored. Results: The pharmacokinetics of ebastine were not modified by renal impairment. No correlation between ebastine pharmacokinetics and renal function, as expressed by CLCR assessed 2 days prior to dosing, was observed. Comparison of the plasma exposure and the elimination half-life of ebastine and carebastine between groups showed no significant differences. Therefore, no apparent accumulation of ebastine and carebastine occurred, and steady-state concentrations of ebastine and carebastine were predictable from single-dose pharmacokinetics for both healthy subjects and patients with renal impairment, even though the variability between the groups was large. In addition, no differences were observed in the safety of ebastine between patients with renal impairment and healthy subjects when assessing adverse events, vital signs, laboratory parameters or ECGs. Conclusion: Ebastine was generally well tolerated in subjects with impaired renal function. No clinically important pharmacokinetic or safety differences were observed between patients with renal impairment and healthy subjects with normal renal function.

AB - Objective: To assess the differences in the pharmacokinetics and cardiac safety of ebastine and its active metabolite, carebastine, in patients with normal and impaired renal function. Methods: Twenty-four patients with varying degrees of renal impairment (mild, moderate or severe: n = 8 per group) and 12 healthy subjects participated in an open-label, parallel-group, multicentre study. Ebastine 20mg was administered orally once daily for 5 days. Plasma concentrations of ebastine and carebastine were determined for 24 hours on day 1 and for 72 hours on day 5 by using a validated sensitive liquid chromatography-tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 ng/mL for ebastine and 1.00 ng/mL for carebastine. Renal function was assessed by measuring 24-hour creatinine clearance (CLCR) at baseline. Cardiac and general safety parameters were also monitored. Results: The pharmacokinetics of ebastine were not modified by renal impairment. No correlation between ebastine pharmacokinetics and renal function, as expressed by CLCR assessed 2 days prior to dosing, was observed. Comparison of the plasma exposure and the elimination half-life of ebastine and carebastine between groups showed no significant differences. Therefore, no apparent accumulation of ebastine and carebastine occurred, and steady-state concentrations of ebastine and carebastine were predictable from single-dose pharmacokinetics for both healthy subjects and patients with renal impairment, even though the variability between the groups was large. In addition, no differences were observed in the safety of ebastine between patients with renal impairment and healthy subjects when assessing adverse events, vital signs, laboratory parameters or ECGs. Conclusion: Ebastine was generally well tolerated in subjects with impaired renal function. No clinically important pharmacokinetic or safety differences were observed between patients with renal impairment and healthy subjects with normal renal function.

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