title: Pharmacokinetics of azithromycin in plasma and sinus mucosal tissue following administration of extended-release or immediate-release formulations in adult patients with chronic rhinosinusitis.
abstract: 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 2g 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 (AUC(24)) for ER was 5.2- and 7.0-fold higher than IR in plasma and sinus tissue, respectively. Comparison between matrices showed that the AUC(24) and AUC(168) in sinus tissue were 28.2- and 62.2-fold higher than in plasma for the ER formulation, whilst the AUC(24) 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.
authors.affiliation: Pfizer Inc, 685 3rd Avenue, M/S 13-48, New York, NY 10017, USA. Annie.F.Fang@pfizer.com
authors.forename: Annie F
authors.initials: AF
authors.lastname: Fang
authors.forename: James N
authors.initials: JN
authors.lastname: Palmer
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Chiu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Blumer
authors.forename: Penelope H
authors.initials: PH
authors.lastname: Crownover
authors.forename: Michael D
authors.initials: MD
authors.lastname: Campbell
authors.forename: Bharat D
authors.initials: BD
authors.lastname: Damle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009831:Olfactory Mucosa / Q000737:chemistry*; D010949:Plasma / Q000737:chemistry*; D012852:Sinusitis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D017963:Azithromycin