Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease

Hohlfeld, Jens M.; Sharma, Ashish; Noord, J.A. van; Cornelissen, P. J. G.; Derom, Eric; Towse, Lesley; Peterkin, Vicky; Disse, Bernd

doi:10.1002/jcph.215

Cited by 58 publications

(72 citation statements)

References 20 publications

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“…The PK profile for tiotropium delivered from TioHH in this study agrees with other published results (20). Absorption after inhalation was rapid with an average t max of 5 min.…”

Section: Discussionsupporting

confidence: 91%

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

Horhota

Noord

Verkleij

et al. 2015

AAPS J

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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, fourway 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 C max,ss . No significant differences in 8-h forced expiratory volume in 1 s or forced vital capacity were detected for the TSHH (qd) against the combination of TioHH (qd) with SalD (bid). Maintenance therapy with tiotropium plus salmeterol as TSHH or as the jointly administered reference products is superior to either agent alone, safe, and well tolerated in COPD patients. In vitro results were not predictive of clinical PK findings for both tiotropium and salmeterol for the TSHH dry powder inhaler product.

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“…The PK profile for tiotropium delivered from TioHH in this study agrees with other published results (20). Absorption after inhalation was rapid with an average t max of 5 min.…”

Section: Discussionsupporting

confidence: 91%

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

Horhota

Noord

Verkleij

et al. 2015

AAPS J

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“…Indeed, there is interesting pharmacokinetic data comparing slow velocity aerosolized solution particles of tiotropium to faster velocity aerosolized powder particles, where blood exposure is lower following the slow velocity aerosol. (157) Part of this may be due to the lower nominal drug dose with the more efficient slower velocity tiotropium aerosol.…”

Section: Importance Of Aerosol Deposition Distribution To Clinical Efmentioning

confidence: 99%

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

Darquenne

Fleming

Katz

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.

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“…The improved efficiency in the delivery of inhaled medication to the lung with Respimat Ò has also allowed reduction of the nominal drug dose without loss of pharmacodynamic effect or clinical efficacy in asthma and COPD [5,[36][37][38][39]. For example, clinical studies in COPD have shown the comparable bronchodilator efficacy and systemic exposure of once-daily tiotropium Respimat Ò 5 lg and tiotropium HandiHaler Ò 18 lg [38,40].…”

Section: Optimizing Drug Delivery To the Lungsmentioning

confidence: 99%

The Respimat® Development Story: Patient-Centered Innovation

et al. 2017

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The Respimat Ò Soft Mist TM Inhaler represents a unique delivery system for respiratory medications, using an innovative concept with major technological advancements made during prototype development. The Respimat Ò concept was driven by the intent to solve problems associated with existing inhaler devices for patient use. The following core aims were achieved: (1) avoiding propellants while reducing requirements for patient coordination and inspiratory effort; (2) optimizing drug delivery to the lungs, and; (3) improving the patients' experience of taking their inhaled medication. The RespimatÒ inhaler is the first-marketed, pocket-sized inhaler to successfully generate a metered dose of therapeutic aerosol mist from an aqueous solution. Patient feedback has strongly influenced the evolution of the Respimat Ò inhaler design and instructions for use. The availability of Respimat Ò augments options for clinicians and patients seeking to choose an inhaler that can effectively and consistently deliver respiratory medication to targeted areas of the lung. In many countries worldwide, Respimat Ò is available for the administration of tiotropium, olodaterol (and tiotropium/olodaterol in fixed-dose combination), ipratropium/fenoterol, and ipratropium/albuterol. Funding: Boehringer Ingelheim.

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Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease

Cited by 58 publications

References 20 publications

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

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

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

The Respimat® Development Story: Patient-Centered Innovation

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