PMID- 23696221
OWN - NLM
STAT- MEDLINE
DCOM- 20150413
LR  - 20131220
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 18
IP  - 6
DP  - 2013
TI  - Safety, tolerability and pharmacokinetics of orally inhaled zanamivir: a 
      randomized study comparing Rotacap/Rotahaler and Rotadisk/Diskhaler in healthy 
      adults.
PG  - 827-30
LID - 10.3851/IMP2631 [doi]
AB  - BACKGROUND: During a pandemic, the need for available anti-influenza medications 
      increases. There has been extensive use of the approved zanamivir 
      Rotadisk/Diskhaler but no clinical data are available for administration by an 
      alternative Rotacap/Rotahaler presentation. METHODS: In this randomized three-way 
      crossover study, each healthy adult received zanamivir 10 mg every 12 h for 5 
      days via Rotadisk/Diskhaler, via Rotacap/Rotahaler and placebo via 
      Rotacap/Rotahaler, with a washout period between treatments. Safety assessments 
      were conducted throughout the study and at follow-up. Serial blood samples for 
      pharmacokinetic analysis were collected over a 12-h dose interval on day 5 of 
      each treatment period. Pharmacokinetic parameters were compared using a 
      mixed-effects model. RESULTS: A total of 18 healthy adults were recruited and 17 
      subjects completed the study. A total of 20 adverse events (AEs) were reported 
      (all grade 1) by nine subjects, with no AE reported >/=1x in any treatment group. 
      Nasal congestion, reported by one subject in the zanamivir Rotadisk/Diskhaler 
      group, was the only drug-related AE. No serious AEs or withdrawals due to AEs 
      occurred during the study. There were no significant changes in clinical 
      laboratory values, vital signs or spirometry. Serum zanamivir exposures were 
      similar after administration via Rotacap/Rotahaler and Rotadisk/Diskhaler. Both 
      oral inhalation presentations are likely to deliver similar zanamivir 
      concentrations to sites of influenza infection in the respiratory tract. 
      CONCLUSIONS: The safety and pharmacokinetic results from this study support the 
      use of the Rotacap/Rotahaler presentation, potentially allowing an increased 
      number of zanamivir treatment courses to be supplied in the event of an influenza 
      pandemic.
FAU - Weller, Stephen
AU  - Weller S
AD  - GlaxoSmithKline, Research Triangle Park, NC, USA. steve.2.weller@gsk.com.
FAU - Jones, Lori S
AU  - Jones LS
FAU - Lou, Yu
AU  - Lou Y
FAU - Piscitelli, Stephen
AU  - Piscitelli S
FAU - Peppercorn, Amanda
AU  - Peppercorn A
FAU - Ng-Cashin, Judith
AU  - Ng-Cashin J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20130521
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Antiviral Agents)
RN  - L6O3XI777I (Zanamivir)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - Antiviral Agents/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Influenza, Human/drug therapy
MH  - Male
MH  - Young Adult
MH  - Zanamivir/*administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2013/05/23 06:00
MHDA- 2015/04/14 06:00
CRDT- 2013/05/23 06:00
PHST- 2013/04/20 00:00 [accepted]
PHST- 2013/05/23 06:00 [entrez]
PHST- 2013/05/23 06:00 [pubmed]
PHST- 2015/04/14 06:00 [medline]
AID - 10.3851/IMP2631 [doi]
PST - ppublish
SO  - Antivir Ther. 2013;18(6):827-30. doi: 10.3851/IMP2631. Epub 2013 May 21.