Pharmacokinetics of azithromycin in plasma and sinus mucosal tissue following administration of extended-release or immediate-release formulations in adult patients with chronic rhinosinusitis

This study compared the pharmacokinetics of azithromycin (AZI) following administration of extended-release (ER) and immediate-release (IR) formulations in plasma and sinus mucosa in patients with chronic rhinosinusitis. Patients (n = 71) were randomised 1:1 to receive a single dose of AZI-ER 2 g or up to three doses of AZI-IR 500 mg daily. Paired plasma and sinus tissue samples were taken during endoscopic sinus surgery at 2-168 h (four patients per time point) after the first dose. Samples were measured by a validated liquid chromatography/mass spectrometry assay. Pharmacokinetics were determined using composite concentration-time profiles. Comparison between formulations showed that within the first 24 h, the AZI area under the plasma concentration-time curve (AUC₂₄) for ER was 5.2- and 7.0-fold higher than IR in plasma and sinus tissue, respectively. Comparison between matrices showed that the AUC₂₄ and AUC₁₆₈ in sinus tissue were 28.2- and 62.2-fold higher than in plasma for the ER formulation, whilst the AUC₂₄ in sinus tissue was 21.1-fold higher than in plasma for IR formulation. These results indicated that AZI has good penetration into sinus tissue regardless of formulation; however, dosing of AZI-ER (2 g) increased AZI exposure within the first 24 h compared with the Day 1 dose of 500 mg IR regimen.