title: Pooled analysis of tiotropium Respimat(®) pharmacokinetics in cystic fibrosis.
abstract: Tiotropium is the first bronchodilator to be studied systematically in cystic fibrosis (CF). We investigated whether any intrinsic or extrinsic factors affected pharmacokinetic (PK) parameters of inhaled tiotropium delivered by Respimat(®) in adults and children with CF. Tiotropium PK in patients with CF was compared with that of healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). This pooled analysis summarizes the PK parameters of inhaled tiotropium Respimat(®) across 9 early- and late-phase trials involving 27 healthy volunteers (1 trial), 409 patients with CF (3 trials), and 281 patients with COPD (5 trials). Patients with CF aged 5 to 11, 12 to 17, and ≥ 18 years had similar tiotropium plasma concentrations (geometric mean C(0.083,ss,norm): 2.22 pg/mL/μg; not determined for patients aged <5 years). The fraction excreted unchanged in the urine was 3.4-fold lower for patients aged 0.4 to <5 years than for those aged 5 to 11 years (fe(0-4,ss): 1.19% vs 4.09%). Tiotropium PK parameters were similar between CF patients and COPD patients.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, Biberach 88400, Germany. Electronic address: ashish.sharma@boehringer-ingelheim.com.
authors.forename: Ashish
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Florida State University College of Medicine, Orlando, FL, USA. Electronic address: degeller2@earthlink.net.
authors.forename: David E
authors.initials: DE
authors.lastname: Geller
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, Ingelheim 55216, Germany. Electronic address: petra.moroni-zentgraf@boehringer-ingelheim.com.
authors.forename: Petra
authors.initials: P
authors.lastname: Moroni-Zentgraf
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Binger Str. 173, Ingelheim 55216, Germany. Electronic address: sabine.kattenbeck@boehringer-ingelheim.com.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kattenbeck
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, Biberach 88400, Germany. Electronic address: marion.schmid@boehringer-ingelheim.com.
authors.forename: Marion
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, Biberach 88400, Germany. Electronic address: katja.boland@boehringer-ingelheim.com.
authors.forename: Katja
authors.initials: K
authors.lastname: Boland
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, Biberach 88400, Germany. Electronic address: barbara.rapp@boehringer-ingelheim.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rapp
authors.affiliation: Rainbow Babies and Children's Hospital and Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: Michael.Konstan@UHhospitals.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto M5G 1X8, Ontario, Canada. Electronic address: felix.ratjen@sickkids.ca.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. Electronic address: s.elborn@qub.ac.uk.
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06776, USA. Electronic address: paul.koker@boehringer-ingelheim.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Koker
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001993:Bronchodilator Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069447:Tiotropium Bromide; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
keywords: Cystic fibrosis; Pharmacokinetics; Respimat(®) inhaler; Tiotropium