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Clinical Pharmacokinetics and Pharmacodynamics of Inhaled Insulin

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Abstract

The benefits of intensive insulin therapy in the prevention of complications in patients with diabetes mellitus are now well established. However, the current methods of insulin administration fall well short of the ideal. Consequently, alternative routes of insulin administration have been investigated. The pulmonary route has received the most attention, helped by advances in inhaler devices and insulin formulation technology. As a result, several insulin inhalation systems are at varying stages of development, with one already filed for marketing approval in Europe.

Knowledge of the pharmacokinetic and pharmacodynamic characteristics of the various inhaled insulin formulations will help to determine their positioning in current and evolving diabetes treatment strategies. For instance, a rapid onset and short duration of action would be desirable for use in postprandial glucose control. Pharmacokinetic studies with inhaled insulin reveal that serum insulin concentrations peak earlier and decay more rapidly following inhalation compared with subcutaneously administered regular insulin, and pharmacodynamic studies measuring glucose infusion rate under euglycaemic glucose clamp show corresponding rapid changes in glucose control. Furthermore, intrapatient variability in the pharmacokinetics and pharmacodynamics of inhaled insulin is low; variability is similar to (or perhaps less than) that seen when insulin is administered subcutaneously. Estimates of the bioavailability and bioefficacy achievable with the current inhalation systems are typically in the region of 10% of that experienced with subcutaneously administered insulin. Most of the losses are in the device, mouth and throat, with ≈30–50% of the insulin deposited in the lungs being absorbed.

Clinical experience to date indicates that inhaled insulin has the potential to be an effective treatment in patients with diabetes, and that it may have particular utility in the treatment of postprandial hyperglycaemia.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

Drs Patton and Eldon are employees of Nektar Therapeutics, the company that has developed the technology for Exubera®. Ms Bukar was an employee of Nektar Therapeutics at the time of preparation of this review.

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  1. Nektar Therapeutics, 150 Industries Road, San Carlos, California, 94070, USA

    John S. Patton & Michael A. Eldon

  2. Rinat Neurosciences, Palo Alto, California, USA

    Julie G. Bukar

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  1. John S. Patton
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Correspondence to John S. Patton.

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Patton, J.S., Bukar, J.G. & Eldon, M.A. Clinical Pharmacokinetics and Pharmacodynamics of Inhaled Insulin. Clin Pharmacokinet 43, 781–801 (2004). https://doi.org/10.2165/00003088-200443120-00002

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