HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Türck, D. Articles by Slowinski, T. Search for Related Content PubMed PubMed Citation Articles by Türck, D. Articles by Slowinski, T. Social Bookmarking                         What's this?

Pharmacokinetics of Intravenous, Single-Dose Tiotropium in Subjects with Different Degrees of Renal Impairment

From the Department of Drug Metabolism and Pharmacokinetics (Dr. Türck, Dr. Rominger), the Department of Medical Data Services (Mr. Sigmund), and the Department Clinical Research (Dr. Feifel), Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riss, Germany; Department of Nephrology, University Hospital Charite, Berlin, Germany (Dr. Slowinski, Dr. Budde, Dr. Neumayer, Dr. Fritsche); and PAREXEL GmbH, Institute of Clinical Pharmacology, Berlin, Germany (Dr. Weber).

Tiotropium, a new potent anticholinergic bronchodilator, is excreted mainly by the kidney. To investigate the pharmacokinetics of tiotropium in renal impairment, the authors evaluated the pharmacokinetics and safety after administration of a single dose of intravenous tiotropium 4.8 µg, given as an infusion over 15 minutes in subjects with normal renal function and a wide range of renal impairment based on measured creatinine clearance (normal: > 80 mL/min, n = 6; mild impairment: > 50-80 mL/min, n = 5; moderate impairment: 30-50 mL/min, n = 7; severe impairment: < 30 mL/min, n =6). As expected for a drug excreted predominantly in unchanged form by the kidneys, tiotropium plasma concentrations increased as renal impairment worsened, with mean values of 55.5 (16.2 percent geometric coefficient of variation [%gCV]), 77.1 (20.1 %gCV), 101 (29.8 %gCV), and 108 (27.3 %gCV) pgh/mL for AUC_0-4h in the normal renal function and the mild, moderate, and severe renal impairment groups, respectively. The percentage of tiotropium dose excreted unchanged in the urine decreased from 60.1% of dose (17.7 %gCV) to 59.3% (14.4 %gCV), 39.9% (34.5 %gCV), and 37.4% (10.2 %gCV) in the normal renal function and the mild, moderate, and severe renal impairment groups, respectively. Plasma protein binding of tiotropium did not significantly change in the renal-impaired subjects. Two subjects with normal renal function experienced headache 10 hours after the infusion, which was mild and transient. No adverse events occurred in subjects with renal impairment. There were no clinically relevant changes in blood pressure, pulse rate, 12-lead ECG, physical examination, hematology, or clinical chemistry, compared with baseline values, in any subject after intravenous administration of tiotropium. Tiotropium should only be used in patients with moderate to severe renal insufficiency if the potential benefit outweighs the potential risks.

Key Words: Tiotropium • chronic obstructive pulmonary disease • renal impairment • pharmacokinetics

Address for reprints: Dr. Dietrich Türck, Boehringer Ingelheim Pharma GmbH & Co KG, Drug Metabolism and Pharmacokinetics Department, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				H. Somand and T. L Remington Tiotropium: A Bronchodilator for Chronic Obstructive Pulmonary Disease Ann. Pharmacother., September 1, 2005; 39(9): 1467 - 1475. [Abstract] [Full Text] [PDF]

				J. L. Olin Tiotropium: An inhaled anticholinergic for chronic obstructive pulmonary disease Am. J. Health Syst. Pharm., June 15, 2005; 62(12): 1263 - 1269. [Abstract] [Full Text] [PDF]