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Pharmacodynamic Studies to Demonstrate Bioequivalence of Oral Inhalation Products

  • Meeting Report
  • Theme: Current Scientific and Regulatory Approaches for Development of Orally Inhaled and Nasal Drug Products
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Abstract

In the session on “Pharmacodynamic studies to demonstrate efficacy and safety”, presentations were made on methods of evaluating airway deposition of inhaled corticosteroids and bronchodilators, and systemic exposure indirectly using pharmacodynamic study designs. For inhaled corticosteroids, limitations of measuring exhaled nitric oxide and airway responsiveness to adenosine for anti-inflammatory effects were identified, whilst measurement of 18-h area under the cortisol concentration–time curve was recommended for determining equivalent systemic exposure. For bronchodilators, methacholine challenge was recommended as the most sensitive method of determining the relative amount of β-agonist or anti-muscarinic agent delivered to the airways. Whilst some agencies, such as the Food and Drug Administration (FDA), do not require measuring systemic effects when pharmacokinetic measurements are feasible, the European Medicines Agency requires measurement of heart rate and serum potassium, and some require serial electrocardiograms when bioequivalence is not established by pharmacokinetic (PK) studies. The Panel Discussion focused on whether PK would be the most sensitive marker of bioequivalence. Furthermore, there was much discussion about the FDA draft guidance for generic fluticasone propionate/salmeterol. The opinion was expressed that the study design is not capable of detecting a non-equivalent product and would require an unfeasibly large sample size.

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Conflicts of Interest

Dr. Hendeles is the PI on research grants to the University of Florida for GlaxoSmithKline, Teva, and Novartis. Dr. Daley-Yates is an employee and shareholder of GlaxoSmithKline. Dr. Hermann received financial support for research from APEPTICO LABORATORIOS CINFA, S.A.; MEDA Pharma, Sun Pharma Advanced Research Company Ltd., Takeda, and Zentiva. Dr. Dissanayake is a full-time employee of Mundipharma Research Limited. Dr. De Backer is founder/shareholder of FLUIDDA. Dr. Horhota is an employee of Boehringer-Ingelheim.

Author information

Authors and Affiliations

  1. Pharmacotherapy and Translational Research and Pediatrics (Pulmonary), University of Florida, PO Box 100486, Gainesville, Florida, 32610-0486, USA

    Leslie Hendeles

  2. Clinical Pharmacology, GlaxoSmithKline, Uxbridge, UK

    Peter T. Daley-Yates

  3. Clinical Research Appliance, Gelnhausen, Germany

    Robert Hermann

  4. FluidDA, Kontich, Belgium

    Jan De Backer

  5. Respiratory Medical Sciences, Mundipharma Research Ltd, Cambridge, UK

    Sanjeeva Dissanayake

  6. Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA

    Stephen T. Horhota

Authors
  1. Leslie Hendeles
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  2. Peter T. Daley-Yates
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  4. Jan De Backer
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  5. Sanjeeva Dissanayake
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  6. Stephen T. Horhota
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Correspondence to Leslie Hendeles.

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Guest Editors: Lawrence Yu, Sau L. Lee, Guenther Hochhaus, Lana Lyapustina, Martin Oliver and Craig Davies-Cutting

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Hendeles, L., Daley-Yates, P.T., Hermann, R. et al. Pharmacodynamic Studies to Demonstrate Bioequivalence of Oral Inhalation Products. AAPS J 17, 758–768 (2015). https://doi.org/10.1208/s12248-015-9735-7

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  • DOI: https://doi.org/10.1208/s12248-015-9735-7

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