PMID- 27022468
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160329
LR  - 20210109
IS  - 2052-1707 (Print)
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 3
IP  - 6
DP  - 2015 Dec
TI  - Inhaled loxapine and intramuscular lorazepam in healthy volunteers: a randomized 
      placebo-controlled drug-drug interaction study.
PG  - e00194
LID - 10.1002/prp2.194 [doi]
LID - e00194
AB  - Pharmacodynamic effects and safety of single-dose inhaled loxapine administered 
      via the Staccato((R)) system and intramuscular (IM) lorazepam in combination versus 
      each agent alone were compared in a randomized, double-blind, crossover study in 
      healthy volunteers. Subjects received: inhaled loxapine 10 mg + IM lorazepam 
      1 mg; inhaled loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato placebo 
      in random order, each separated by a 3-day washout. Primary endpoints were 
      maximum effect (minimum value) and area under the curve (AUC) from baseline to 
      2 h post treatment for respirations/min and pulse oximetry. Least-squares means 
      (90% confidence interval [CI]) for concomitant treatment versus each agent alone 
      were derived and equivalence (no difference) confirmed if the 90% CI was within 
      0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual analog 
      scale), and adverse events (AEs) were recorded. All 18 subjects (mean age, 
      20.4 years; 61% male) completed the study. There was no difference between 
      inhaled loxapine + IM lorazepam and either agent alone on respiration or pulse 
      oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min 
      ratios. BP and HR were no different for inhaled loxapine + IM lorazepam and each 
      agent alone over a 12-h postdose period. Although the central nervous system 
      sedative effects were observed for each treatment in healthy volunteers, the 
      effect was greater following concomitant lorazepam 1 mg IM + inhaled loxapine 
      10 mg administration. There were no deaths, serious AEs, premature 
      discontinuations due to AEs, or treatment-related AEs.
FAU - Spyker, Daniel A
AU  - Spyker DA
AD  - Alexza Pharmaceuticals, Inc. Mountain View California.
FAU - Cassella, James V
AU  - Cassella JV
AD  - Alexza Pharmaceuticals, Inc. Mountain View California.
FAU - Stoltz, Randall R
AU  - Stoltz RR
AD  - Covance Clinical Research Unit Evansville Indiana.
FAU - Yeung, Paul P
AU  - Yeung PP
AD  - Teva Pharmaceuticals Frazer Pennsylvania.
LA  - eng
PT  - Journal Article
DEP - 20151217
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
PMC - PMC4777253
OTO - NOTNLM
OT  - Bipolar I disorder
OT  - drug-drug interactions
OT  - inhaled loxapine
OT  - lorazepam
OT  - pharmacodynamics
OT  - schizophrenia
EDAT- 2016/03/30 06:00
MHDA- 2016/03/30 06:01
PMCR- 2015/12/17
CRDT- 2016/03/30 06:00
PHST- 2015/09/10 00:00 [received]
PHST- 2015/09/17 00:00 [accepted]
PHST- 2016/03/30 06:00 [entrez]
PHST- 2016/03/30 06:00 [pubmed]
PHST- 2016/03/30 06:01 [medline]
PHST- 2015/12/17 00:00 [pmc-release]
AID - PRP2194 [pii]
AID - 10.1002/prp2.194 [doi]
PST - epublish
SO  - Pharmacol Res Perspect. 2015 Dec 17;3(6):e00194. doi: 10.1002/prp2.194. 
      eCollection 2015 Dec.