Background and ObjectivesThe 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.MethodsIn 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.ResultsFor 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 ½) ~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 ½ ~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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-017-0549-5) contains supplementary material, which is available to authorized users.

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Abstract. The nature of the interface between CuInSe 2 (CIS) and the chemical bath deposited CdS layer has been investigated. We show that heat-treating the absorbers in Cd-or Zn-containing solutions in the presence of ammonium hydroxide sets up a chemical reaction which facilitates an extraction of Cu from the lattice and an in-diffusion of Cd. The characteristics of devices made in this manner suggest that the reaction generates a thin, n-doped region in the absorber. It is quite possible that the CdS/CuInSe 2 device is a buried, shallow junction with a CdS window layer, rather than a heterojunction. We have used these ideas to develop methods for fabricating devices without CdS or Cd. A 14.2% efficiency ZnO/CIGS device was obtained through aqueous treatment in Zn solutions.

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