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J Aerosol Med Pulm Drug Deliv. 2014 Jun;27(3):178-84. doi: 10.1089/jamp.2013.1042. Epub 2013 May 13.

Lung deposition and pharmacokinetics of nebulized cyclosporine in lung transplant patients.

Author information

1
1 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh , Pittsburgh, PA 15213.

Abstract

BACKGROUND:

Inhaled cyclosporine (CsA) is being investigated as a prophylaxis for lung transplant rejection. Lung deposition and systemic exposure of nebulized CsA in lung transplant patients was evaluated as part of the Phase 3 cyclosporine inhalation solution (CIS) trial (CYCLIST).

METHODS:

Ten patients received 300 mg of CIS (62.5 mg/mL CsA in propylene glycol) admixed with 148 MBq of Tc-DTPA (technetium-99m bound to diethylenetriaminepentaacetic acid) administered using a Sidestream(®) disposable jet nebulizer. Deposition was assessed using a dual-headed gamma camera. Blood samples were collected over a 24-hr time period after aerosol dosing and analyzed for CsA levels. A pharmacokinetic analysis of the resulting blood concentration versus time profiles was performed.

RESULTS:

The average total deposited dose was 53.7 ± 12.7 mg. Average pulmonary dose was 31.8 ± 16.3 mg, and stomach dose averaged 15.5 ± 11.1 mg. Device performance was consistent, with breathing maneuvers influencing dose variation. Predose coaching with five of 10 patients reduced stomach deposition (22.6 ± 11.2 vs. 8.3 ± 5.2 mg; p=0.03). Blood concentrations declined quickly from a maximum of 372 ± 140 ng/mL to 15.3 ± 9.7 ng/mL at 24 hr post dose. Levels of AUC(0-24) [area under the concentration vs. time curve from 0 to 24 hr] averaged 1,493 ± 746 ng hr/mL. On a three times per week dose regimen, this represents <5% of the weekly systemic exposure of twice per day oral administration.

CONCLUSIONS:

Substantial doses of CsA can be delivered to the lungs of lung transplant patients by inhaled aerosol. Systemic levels are small relative to typical oral CsA administration.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00755781.

KEYWORDS:

aerosol deposition; inhaled cyclosporine; lung transplant

PMID:
23668548
PMCID:
PMC4088352
DOI:
10.1089/jamp.2013.1042
[Indexed for MEDLINE]
Free PMC Article

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