Figure 2.

AZD5634 shows a dose-dependent increase of sheep MCC and a good duration of effect. A: for the dose-response evaluation, AZD5634 was administered just before the inhalation of ^99mTc. AZD5634 at 1–330 µg/kg demonstrates a dose-dependent increase of MCC (no stats performed due to the low n-numbers in the present model) with a max effect achieved at 120 µg/kg. B: for the evaluation of duration, the submaximal dose of 12 µg/kg AZD5634 was administered 0, 4, 8, 12, and 24 h before the ^99mTc administration. The retention of colloids was in all cases evaluated for 60 min after the administration of ^99mTc. C: repeated dosing of 3 μg/kg AZD5634 bid for 4 days (i.e., 7 doses) resulted in similar efficacy on MCC in sheep as 12 μg/kg 8 h after dosing. D: ^99mTc clearance of AZD5634 as a function of time as assessed by linear regression. The pharmacokinetic half-life of efficacy was estimated to be 9–10 h (marked with a star). Individual data are shown on the regression line, with the dotted line representing the mean clearance of vehicle-treated animals. n = 2–3 animals per group. MCC, mucociliary clearance.