Pharmacokinetic and Pharmacodynamic Evaluation of Liposomal Amikacin for Inhalation in Cystic Fibrosis Patients with Chronic Pseudomonal Infection.

: Antimicrob Agents Chemother. 2009 May 18. [Epub ahead of print]

Pharmacokinetic and Pharmacodynamic Evaluation of Liposomal Amikacin for Inhalation in Cystic Fibrosis Patients with Chronic Pseudomonal Infection.

Okusanya OO, Bhavnani SM, Hammel J, Minic P, Dupont LJ, Forrest A, Mulder GJ, Mackinson C, Ambrose PG, Gupta R.

Institute for Clinical Pharmacodynamics, Ordway Research Institute, Inc., Albany, New York; Institute for Mother and Child Healthcare, Beograd, Serbia; Department of Respiratory Medicine, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium; Forbion Capital Partners, Naarden, The Netherlands; Transave, Inc., Monmouth Junction, New Jersey.

The pharmacokinetics and pharmacodynamics of a novel liposomal amikacin for inhalation were evaluated in cystic fibrosis patients with chronic pseudomonas infection. Twenty-four patients from 2 studies received liposomal amikacin 500 mg by inhalation once daily for 14 days. Serum, sputum and 24 hour urine samples were collected on Days 1 and 14 of therapy; pulmonary function tests (PFT) and sputum for quantitative microbiology were assessed at baseline and serially for 14 days.

Relationships between amikacin exposure in serum and sputum and absolute change in PFT endpoints and log10 colony forming units (CFU) of Pseudomonas aeruginosa from baseline on Days 7 and 14 of therapy were assessed. On Days 7 and 14, absolute change from baseline in forced expiratory volume in one second (FEV1), percent predicted forced expiratory volume in one second (FEV1%predicted) and forced expiratory flow between 25-75% of forced vital capacity (FEF25-75%) increased by 0.24 (p = 0.002) and 0.13L (p = 0.10), 7.49 (p < 0.001) and 4.38 (p = 0.03), 0.49 (p < 0.001) and 0.42 (p = 0.02) L/sec, respectively. In addition, relative change from baseline in FEV1%predicted was 10.8% (p < 0.001) and 5.62% (p = 0.073) on Days 7 and 14, respectively.

While significant relationships between absolute change in PFT endpoints and the ratio of serum or sputum area under the concentration-time curve to the minimum inhibitory concentration (AUC:MIC) ratio were not observed, relationships between change in log10CFU and serum AUC:MIC ratio, and change in log10CFU and absolute changes in all PFT endpoints were significant. Together, these findings likely represent drug effect and warrant the further development of liposomal amikacin for inhalation.

PMID: 19451281 [PubMed - as supplied by publisher]