PMID- 28856569
OWN - NLM
STAT- MEDLINE
DCOM- 20180416
LR  - 20181202
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Print)
IS  - 1173-2563 (Linking)
VI  - 37
IP  - 11
DP  - 2017 Nov
TI  - Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers.
PG  - 1025-1034
LID - 10.1007/s40261-017-0549-5 [doi]
AB  - BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being 
      investigated as a treatment for early Alzheimer's disease (AD). This study 
      investigated the pharmacokinetics, safety, and tolerability of cromolyn and 
      ibuprofen co-administration in healthy elderly adult volunteers. METHODS: In this 
      open-labeled study, 26 subjects, aged 55-75 years, received co-administration of 
      inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral 
      ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was 
      performed for 6 h after co-administration in all subjects; cerebrospinal fluid 
      (CSF) was collected in three to four subjects per cohort for 4 h following 
      co-administration. Safety parameters, including adverse events (AEs), were 
      monitored throughout the study. RESULTS: For cromolyn, the mean (+/-SD) maximum 
      observed concentration (C (max)) in plasma was 46.69 +/- 32.97 and 96.75 +/- 
      46.22 ng/ml after single- and double-dose inhalation, respectively [time to C 
      (max) (t (max)) ~22 min for each; terminal elimination half-life (t ((1/2))) ~1.8 h 
      for each]. For ibuprofen, the plasma C (max) was 1090.98 +/- 474.64 ng/ml and 
      2062.96 +/- 655.13 ng/ml after single- and double-dose oral administration, 
      respectively (t (max) ~1.6-1.8 h; t ((1/2)) ~1.9 h for each). For cromolyn, the CSF C 
      (max) was 0.24 +/- 0.08 ng/ml at 3.72 +/- 0.70 h after single-dose administration and 
      0.34 +/- 0.17 ng/ml at 3.45 +/- 0.95 h after double-dose administration, and for 
      ibuprofen, the CSF C (max) was 3.94 +/- 1.29 ng/ml at 2.55 +/- 0.96 h after 
      single-dose administration and 8.93 +/- 3.29 ng/ml at 3.15 +/- 1.05 h after 
      double-dose administration. Three (12%) subjects reported mild or moderate AEs 
      which were unlikely to be related to study drug. CONCLUSIONS: The combination of 
      cromolyn and ibuprofen was safe and well tolerated. The concentrations of 
      cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate 
      the estimated daily amyloid production and the associated inflammatory response 
      in patients with AD.
FAU - Brazier, David
AU  - Brazier D
AD  - AZTherapies, Inc, 222 Berkeley Street, 12th Floor, Boston, MA, 02116, USA.
FAU - Perry, Robert
AU  - Perry R
AD  - Panax Clinical Research, Miami Lakes, FL, USA.
FAU - Keane, Jim
AU  - Keane J
AD  - AZTherapies, Inc, 222 Berkeley Street, 12th Floor, Boston, MA, 02116, USA.
FAU - Barrett, Katie
AU  - Barrett K
AD  - AZTherapies, Inc, 222 Berkeley Street, 12th Floor, Boston, MA, 02116, USA.
FAU - Elmaleh, David R
AU  - Elmaleh DR
AD  - AZTherapies, Inc, 222 Berkeley Street, 12th Floor, Boston, MA, 02116, USA. 
      delmaleh@aztherapies.com.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - Q2WXR1I0PK (Cromolyn Sodium)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Alzheimer Disease/drug therapy
MH  - Cromolyn Sodium/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Ibuprofen/*pharmacokinetics
MH  - Male
MH  - Middle Aged
PMC - PMC5643367
COIS- FUNDING: This study was funded by AZ Therapies, Inc. CONFLICTS OF INTEREST: David 
      Brazier, Jim Keane, Katie Barrett, and David R. Elmaleh are employees of the 
      study sponsor, AZ Therapies, Inc. Robert Perry is an employee of Panax Clinical 
      Research, the site of the clinical study. ETHICS APPROVAL: The study was approved 
      in writing on 16-APR-2015 by the Liberty Institutional Review Board (IRB) in 
      DeLand, FL, USA. All study procedures were in accordance with the 1964 Helsinki 
      declaration (and its amendments). INFORMED CONSENT: The subject informed consent 
      (IC) was reviewed and approved by the IRB for the study. The formal consent of a 
      subject, using the IRB-approved consent form, was obtained before the subject 
      underwent any study procedure. The IC was signed by the subject and the 
      investigator/designated research professional obtaining the consent. Subjects 
      willing to allow lumbar puncture for CSF collection were also consented using a 
      procedure-specific IC.
EDAT- 2017/09/01 06:00
MHDA- 2018/04/17 06:00
PMCR- 2017/08/30
CRDT- 2017/09/01 06:00
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2018/04/17 06:00 [medline]
PHST- 2017/09/01 06:00 [entrez]
PHST- 2017/08/30 00:00 [pmc-release]
AID - 10.1007/s40261-017-0549-5 [pii]
AID - 549 [pii]
AID - 10.1007/s40261-017-0549-5 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2017 Nov;37(11):1025-1034. doi: 10.1007/s40261-017-0549-5.