Pharmacokinetics and biomarker induction following a single inhaled dose of AZD8848 in man.(A) Plasma concentration-time profiles of AZ12432045, the acid.

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Presentation transcript:

Pharmacokinetics and biomarker induction following a single inhaled dose of AZD8848 in man.(A) Plasma concentration-time profiles of AZ12432045, the acid metabolite of AZD8848, following a single predicted lung-deposited dose of AZD8848 as indicated in the ... Pharmacokinetics and biomarker induction following a single inhaled dose of AZD8848 in man.(A) Plasma concentration-time profiles of AZ12432045, the acid metabolite of AZD8848, following a single predicted lung-deposited dose of AZD8848 as indicated in the key. The predicted lung-deposited dose was assumed to be 63% of the dose delivered from the nebuliser. During sample preparation, any trace amounts of AZD8848 were hydrolysed by esterases in the plasma. All cohorts were administered by nebulisation taken in 10 breaths as described in Methods section. No data are shown for cohort 1 (0.15 µg) as levels of AZ12432045 were below the level of detection. Values shown are geometric means (±SD) from 3 to 5 individuals in each cohort. (B) CXCL10 was determined in induced sputum (black) and in plasma (grey) of healthy volunteers for the indicated predicted lung-deposited dose of AZD8848. The fold change at 24 h postdose from baseline for individual participants is shown. Geometric mean is shown in each cohort and significance relative to placebo (p<0.05) is indicated on the basis of analysis of covariance (ANCOVA) analyses with baseline as a covariate. RNA changes for CCL8 (C), MX2 (D) CCL2 (E) and IFIT2 (F) were determined in induced sputum cells using quantitative RT-PCR. Geometric means are shown in each cohort and significance relative to placebo, *p<0.05, is indicated on the basis of two-sample Student t-tests. Stephen Delaney et al. BMJ Open Resp Res 2016;3:e000113 ©2016 by British Thoracic Society