title: Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34).
abstract: Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the morning after an overnight fast and blood samples for measurement of PTH(1 - 34), PTH(1 - 84), and calcium and calcitonin were taken over a period of 6 hours. Both injection and pulmonary application of PTH(1 - 34) were well tolerated. After pulmonary administration of Technosphere/PTH(1 - 34), PTH(1 - 34) appeared in the serum with a faster concentration increase (T max: pulmonary 10 +/- 5 min vs. subcutaneous 28 +/- 8 min, p < 0.001) and with higher maximal concentrations (C max : pulmonary 309 +/- 215 pmol/l vs. subcutaneous 102 +/- 45 pmol/l, p < 0.05) as compared to the subcutaneous injection. The relative bioavailability of pulmonary Technosphere/PTH(1 - 34) was calculated to be 48 %. No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density.
authors.affiliation: MannKind Biopharmaceuticals, 1 Casper Street, Danbury, CT, USA. AndreasP@IKFE.de
authors.forename: A
authors.initials: A
authors.lastname: Pfützner
authors.forename: F
authors.initials: F
authors.lastname: Flacke
authors.forename: R
authors.initials: R
authors.lastname: Pohl
authors.forename: D
authors.initials: D
authors.lastname: Linkie
authors.forename: M
authors.initials: M
authors.lastname: Engelbach
authors.forename: R
authors.initials: R
authors.lastname: Woods
authors.forename: T
authors.initials: T
authors.lastname: Forst
authors.forename: J
authors.initials: J
authors.lastname: Beyer
authors.forename: S S
authors.initials: SS
authors.lastname: Steiner
mesh_terms: D000328:Adult; D001682:Biological Availability; D002116:Calcitonin / Q000097:blood; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008863:Microspheres; D010865:Pilot Projects; D019379:Teriparatide / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D019379:Teriparatide; D002116:Calcitonin; D002118:Calcium