In Vitro, Pharmacokinetic, Pharmacodynamic, and Safety Comparisons of Single and Combined Administration of Tiotropium and Salmeterol in COPD Patients Using Different Dry Powder Inhalers

The AAPS Journal
Stephen T HorhotaP J G Cornelissen

Abstract

In vitro Andersen cascade impactor-sized mass (ISM) and aerodynamic fine particle mass (FPM) <5 μm for tiotropium and salmeterol combined in a novel inhalation powder formulation containing 7.5 μg tiotropium/25 μg salmeterol (TSHH) were similar (within ±15%) to reference products containing 18 μg of tiotropium (Spiriva® HandiHaler®) (TioHH) and 50 μg of salmeterol (Serevent® Diskus®) (SalD). The pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of the novel fixed-dose TSHH formulation administered once daily was compared with the single-agent therapies TioHH (once daily [qd]) and SalD (twice daily [bid]) and with the jointly administered combination of TioHH (qd) plus SalD (bid) in a randomized, 22-week, open-label, four-way crossover study in 50 patients with chronic obstructive pulmonary disease (COPD). For tiotropium, TSHH and TioHH were bioequivalent based on mean steady-state plasma area under the plasma concentration-time curves (AUC), while the urinary excretion amount was higher for TSHH and not bioequivalent to TioHH. Tiotropium peak plasma concentrations at steady state (C max,ss) were 40% higher with TSHH. For salmeterol, substantial differences were observed in plasma AUCs and Cmax,ss. No significant...Continue Reading

References

Sep 1, 1995·American Journal of Respiratory and Critical Care Medicine
Mar 29, 2001·International Journal of Pharmaceutics·A Jouyban-GharamalekiB J Clark
Feb 5, 2002·Clinical Pharmacokinetics·Mario CazzolaMaria Gabriella Matera
Dec 15, 2004·Chest·Nicholas J Gross
Mar 15, 2006·Apoptosis : an International Journal on Programmed Cell Death·P SanchoP Aller
Feb 6, 2010·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Wallace P AdamsLawrence Yu
Mar 23, 2010·Respiratory Medicine·J A van NoordP J G Cornelissen
Dec 8, 2010·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Peter R ByronWarren H Finlay
Apr 2, 2011·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Dennis O'ConnorSandra Suarez Sharp
Mar 15, 2012·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Carole EvansPatricia Watson
Nov 10, 2012·The AAPS Journal·Benjamin Weber, Guenther Hochhaus
May 9, 2013·Respiratory Research·Donald P Tashkin, Gary T Ferguson
Jan 5, 2014·American Journal of Respiratory and Critical Care Medicine·Paul W JonesJadwiga A Wedzicha

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Citations

Apr 5, 2017·Biopharmaceutics & Drug Disposition·Konstantina SouleleVangelis Karalis
Jul 15, 2017·Journal of Aerosol Medicine and Pulmonary Drug Delivery·Irvin Mayers, Mohit Bhutani
Sep 19, 2017·Expert Opinion on Drug Delivery·Irvin Mayers, Mohit Bhutani
Dec 7, 2019·Therapeutic Advances in Respiratory Disease·Federico LavoriniAnders Løkke
Aug 31, 2021·Advanced Drug Delivery Reviews·Michael Yee Tak ChowPhilip Chi Lip Kwok
Oct 19, 2021·Experimental and Therapeutic Medicine·Hiroko OtakeNoriaki Nagai

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