A gamma scintigraphy study to investigate lung deposition and clearance of inhaled amikacin-loaded liposomes in healthy male volunteers

Weers, Jeffry, Metzheiser, Beth, Taylor, Glyn, Warren, Simon J., Meers, Paul and Perkins, Walter R. 2009. A gamma scintigraphy study to investigate lung deposition and clearance of inhaled amikacin-loaded liposomes in healthy male volunteers. Journal of Aerosol Medicine and Pulmonary Drug Delivery 22 (2) , pp. 131-138. 10.1089/jamp.2008.0693

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Abstract

Background: The purpose of this study was to investigate the inhalation of a liposomal formulation of amikacin in healthy male volunteers in terms of pulmonary deposition, clearance, and safety following nebulization with a commercial jet nebulizer. Methods: Amikacin was encapsulated in liposomes comprised of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol via a proprietary manufacturing process (20 mg/mL final amikacin concentration). The liposomes were radiolabeled with 99mTc using the tin chloride labeling method. A nominal dose of 120 mg of drug product was loaded into a PARI LC STAR nebulizer, aerosolized using a PARI Boy compressor where subjects inhaled for 20 min. Lung deposition was determined by gamma scintigraphy in three healthy male volunteers at the following time points (0, 1, 3, 6, 12, 24, 48, and 72 h post-administration). Results: Total lung deposition, expressed as a percentage of the emitted dose, was 32.3 � 3.4%. The time-dependent retention of radiolabeled liposomes was biphasic with an initial rapid reduction in counts, followed by a slower phase to 48 h. The overall mean retention at 24 and 48 h was 60.4 and 38.3% of the initial dose deposited, respectively. The observed clearance of radiolabel is consistent with clearance of amikacin following aerosol delivery to rats. There were no clinically significant changes in laboratory parameters, vital signs, or ECG. No adverse events including cough or bronchospasm were reported. Conclusions: Inhalation of a single nominal dose of 120 mg liposomal amikacin results in prolonged retention of drug-loaded liposomes in the lungs of healthy volunteers. The treatment was well tolerated.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	aerosol distribution ; amikacin ; sustained release; liposomes ; inhalation
Publisher:	Mary Ann Liebert
ISSN:	1941-2711
Last Modified:	04 Jun 2017 01:58
URI:	https://orca.cardiff.ac.uk/id/eprint/6766

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