Universität zu Köln

van Koningsbruggen-Rietschel, S., Heuer, H. E., Merkel, N., Posselt, H. G., Staab, D., Sieder, C., Ziegler, J., Krippner, F. and Rietschel, E. (2016). Pharmacokinetics and safety of an 8 week continuous treatment with once-daily versus twice-daily inhalation of tobramycin in cystic fibrosis patients. J. Antimicrob. Chemother., 71 (3). S. 711 - 718. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

Full text not available from this repository.

Abstract

This randomized, multicentre, open-label, two-period crossover study showed that inhaling tobramycin either once daily or twice daily for 8 weeks appears to be safe and tolerable for treating patients with cystic fibrosis and chronic P. aeruginosa infection.We evaluated the pharmacokinetics, safety and tolerability of two different continuous treatment regimens of tobramycin inhalation solution (TIS) in 29 cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. In this randomized, multicentre, open-label, two-period crossover study, TIS (300 mg/5 mL) was administered via PARI eFlow(A (R)) rapid once daily and twice daily each for 8 weeks. Serum pharmacokinetics of these two regimens was analysed. Tobramycin levels were determined before the morning dose and at 30, 60 and 90 min after the end of nebulization in the middle and at the end of each 8 week cycle. At these timepoints, trough and peak serum tobramycin concentrations (C-max, mg/L) as well as the area under the curve for 0-90 min of tobramycin (AUC(0-90min)) were assessed in order to evaluate the risk of systemic toxicity. Safety parameters and forced expiratory volume in 1 s (FEV1) were assessed. For once-daily treatment, tobramycin levels were 10% higher after 8 weeks compared with 4 weeks (AUC(0-90min) ratioaEuroS=aEuroS1.096, 90% CIaEuroS=aEuroS0.860-1.396, PaEuroS=aEuroS0.5237). For twice-daily treatment, tobramycin levels after 8 weeks showed a 40% decrease compared with 4 weeks (AUC(0-90min) ratioaEuroS=aEuroS0.608, 90% CIaEuroS=aEuroS0.461-0.802, PaEuroS=aEuroS0.0055). The AUC(0-90min) ratio at 8 weeks (once daily versus twice daily) did not differ significantly (AUC(0-90min) ratioaEuroS=aEuroS0.749, 90% CIaEuroS=aEuroS0.514-1.092, PaEuroS=aEuroS0.2009). The mean FEV1 did not differ markedly compared between treatment periods or with baseline. No audiological or nephrotoxic side effects were noted. Continuous treatment with TIS (once daily or twice daily) over 8 weeks appears to be safe and tolerable.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Koningsbruggen-Rietschel, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heuer, H. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkel, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Posselt, H. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Staab, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sieder, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziegler, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krippner, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-282668
DOI:	10.1093/jac/dkv399
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	71
Number:	3
Page Range:	S. 711 - 718
Date:	2016
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PSEUDOMONAS-AERUGINOSA INFECTION; INHALED TOBRAMYCIN; YOUNG-CHILDREN; AEROSOLIZED TOBRAMYCIN; LUNG-DISEASE; SERUM Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28266