Pharmacokinetic Characterization of the Novel Pulmonary Delivery Excipient Fumaryl Diketopiperazine

Background: Technosphere® [Bis-3, 6(4-fumarylaminobutyl)-2, 5-diketopiperazine (FDKP)] microparticles, the integral component of the Technosphere inhalation system, deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies....

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Bibliographic Details
Published in:Journal of diabetes science and technology 2010-09, Vol.4 (5), p.1164-1173
Main Authors: Potocka, Elizabeth, Cassidy, James P., Haworth, Pamela, Heuman, Douglas, van Marle, Sjoerd, Baughman, Robert A.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Adult
Aged
Chronic Disease
Diabetic Neuropathies - metabolism
Drug Delivery Systems - adverse effects
Drug Delivery Systems - methods
Excipients - administration & dosage
Excipients - pharmacokinetics
Female
Fumarates - administration & dosage
Fumarates - pharmacokinetics
Humans
Injections, Intravenous
Kidney - metabolism
Liver Diseases - metabolism
Male
Microspheres
Middle Aged
Original
Piperazines - administration & dosage
Piperazines - pharmacokinetics
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Summary:Background: Technosphere® [Bis-3, 6(4-fumarylaminobutyl)-2, 5-diketopiperazine (FDKP)] microparticles, the integral component of the Technosphere inhalation system, deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies. Three studies were conducted to characterize FDKP pharmacokinetics, including assessments in subjects with diabetic nephropathy (DNP), in subjects with chronic liver disease (CLD), and in healthy subjects. Methods: An open-label, nonrandomized, two-period, fixed-sequence crossover absorption, distribution, metabolism, and excretion (ADME) study was conducted in six healthy nonsmoking men who received single intravenous and oral doses of [14C]FDKP solution, with serial sampling of blood, urine, feces, and expired air. Additionally, two single-dose, open-label, parallel-design studies with 20 mg of inhaled FDKP were conducted in (1) 12 diabetic subjects with normal renal function and 24 DNP subjects and (2) 12 healthy subjects and 21 CLD subjects. Results: In the ADME study, >95% of the intravenous dose and
ISSN:1932-2968
1932-2968
1932-3107
DOI:10.1177/193229681000400515