PMID- 15541915
OWN - NLM
STAT- MEDLINE
DCOM- 20050222
LR  - 20131121
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 287
IP  - 1-2
DP  - 2004 Dec 9
TI  - An investigation into the predictive value of cascade impactor results for side 
      effects of inhaled salbutamol.
PG  - 79-87
AB  - The aim of this study was to compare the Multistage Liquid Impinger (MSLI) and 
      the Andersen Cascade Impactor (ACI) with respect to their power to predict 
      differences in side effects of salbutamol delivered by a dry powder inhaler. 
      Three preparations with the same nominal dose and the same inhaler device but 
      generating aerosols with different aerodynamic particle size distributions were 
      administered to six healthy volunteers in a randomized, placebo-controlled, 
      four-way crossover study. Cumulative doses from 400 up to 1600 microg were given. 
      The serum potassium level (K+-serum) and the heart rate (HR) were measured at 
      baseline and 15 min after each dose. Both the MSLI and ACI showed large 
      differences between the aerodynamic particle size distributions of the three 
      preparations. The decrease in K+-serum revealed significant differences between 
      the three active preparations and was significant for doses of 800 microg and 
      higher. The HR results showed differences between the active preparations only at 
      a nominal dose of 1600 microg and only for the preparation with the highest fine 
      particle dose (FPD) compared to the other two preparations. The K+-serum appears 
      to be a more sensitive measure for side effects than the HR. In vivo-in vitro 
      correlations (IVIVCs) were established between the amounts of salbutamol 
      deposited on the various cumulative impactor stages and the K+-serum. The best 
      IVIVCs were obtained in the FPD range, resulting in correlation coefficients of 
      at least 0.78. It is concluded that cascade impactor results in the FPD range of 
      the MSLI as well as the ACI correlate well with the K+-serum. Cascade impactor 
      analysis thus provides a clinically meaningful tool in the development and the 
      quality control of salbutamol inhalation powders.
FAU - Weda, M
AU  - Weda M
AD  - National Institute for Public Health and the Environment, Centre for Quality of 
      Chemical-Pharmaceutical Products, Postbak 40, P.O. Box 1, 3720 BA Bilthoven, The 
      Netherlands. marjolein.weda@rivm.nl
FAU - Zanen, P
AU  - Zanen P
FAU - de Boer, A H
AU  - de Boer AH
FAU - Barends, D M
AU  - Barends DM
FAU - Frijlink, H W
AU  - Frijlink HW
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - QF8SVZ843E (Albuterol)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - Albuterol/administration & dosage/*adverse effects
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Potassium/blood
EDAT- 2004/11/16 09:00
MHDA- 2005/02/23 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/03/23 00:00 [received]
PHST- 2004/07/13 00:00 [revised]
PHST- 2004/08/26 00:00 [accepted]
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2005/02/23 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - S0378-5173(04)00515-0 [pii]
AID - 10.1016/j.ijpharm.2004.08.017 [doi]
PST - ppublish
SO  - Int J Pharm. 2004 Dec 9;287(1-2):79-87. doi: 10.1016/j.ijpharm.2004.08.017.