Document Detail

Single-dose and multi-dose delivery systems for intranasal fentanyl spray are bioequivalent as demonstrated in a replicate pharmacokinetic study.
MedLine Citation:
PMID:  22943926     Owner:  NLM     Status:  Publisher    
Background: Intranasal fentanyl spray (INFS, Instanyl®) was developed to treat cancer patients with Breakthrough Pain (BTP). INFS is delivered via a multi-dose delivery system (MDS) that is available in various dose strengths. The aim of this study was to demonstrate the pharmacokinetic bioequivalence of INFS single dose delivery system (SDS) in relation to the currently marketed MDS device. Methods: In a randomized, single-center, single-dose, open label, comparative, four-period, two-sequence, replicate cross-over study, 48 healthy subjects (24 male and 24 female, mean age of 28.1 years, mean bodyweight 69.8 kg) received 200 μg/100 μl fentanyl administered via SDS and via MDS in one of two alternating treatment sequences. Naltrexone was given to all subjects to prevent potential fentanyl adverse drug reactions. Blood samples were frequently taken up to 72 hours post INFS administration and analyzed by liquid chromatography with tandem mass spectrometric detection. Primary pharmacokinetic parameters were area under the curve extrapolated to infinity (AUC0-∞) and peak plasma concentration (Cmax). Statistical analyses of the primary pharmacokinetic parameters were performed using a linear mixed effect model applied to the natural log-transformed data. Results: Healthy subjects showed very similar plasma concentration over time profiles for both delivery systems. The mean fentanyl Cmax and AUC0-∞ values for SDS and MDS were 948 pg/ml, 949 pg/ml and 4,439 pg×h/ml, 4,489 pg×h/ml. respectively. Point estimates (and 90% confidence intervals) for AUC and Cmax were 0.97 (0.93 - 1.02) and 1.00 (0.92 - 1.09) and therefore in the bioequivalence range of 0.80 - 1.25. Conclusions: Results of this study show that SDS and MDS met the pre-defined regulatory criteria for bioequivalence. Safety profiles were consistent between both devices and no safety concerns were identified with INFS administered in combination with oral naltrexone.
Rüdiger Nave; Sandra M Connolly; Lars Popper; Gezim Lahu; Holger Schmitt
Related Documents :
7139856 - Nitrosamine-induced pancreatic carcinogenesis in outbred and inbred syrian hamsters.
24191286 - Human interventions to characterize novel relationships between the renin-angiotensin-a...
10791186 - Effect of omeprazole on gallbladder contraction in humans.
2916886 - Limited weight losses with a gastric balloon.
20300986 - Investigation of source position uncertainties & balloon deformation in mammosite brach...
2242726 - Target animal safety test of a dexamethasone-prednisolone combination in horses.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-4
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  -     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung ...
Next Document:  Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cyto...