title: Pharmacokinetics and sputum penetration of azithromycin during once weekly dosing in cystic fibrosis patients.
abstract: In this study we examined pharmacokinetics, systemic exposure and sputum penetration of azithromycin (AZM) in CF patients on chronic daily AZM therapy after changing to a once weekly dosing scheme. Eight adult CF patients using AZM 500 mg/day were changed to a once weekly dose of 1000 mg during 3 months. Once per month sputum and blood samples were collected. AZM was quantified in blood plasma and polymorphonuclear neutrophils. The cumulative weekly dose was reduced with a factor of 3.5 (7x500 mg vs. 1x1000 mg weekly). This led to a reduction in area under the curve (AUC+/-S.D.) with a factor of 2.5+/-0.8 in plasma, 2.8+/-0.9 in blood, 2.2+/-1.1 in PMNNs and to a reduction in average sputum concentration with a factor of 3.0 (+/-1.5). At 1000 mg once weekly reduced but still substantial concentrations were achieved in PMNNs and in sputum. Although not significant, a tendency towards less than linear reduction was found. In order to calculate and propose an optimal dosing scheme we need to establish a relation between exposure levels and clinical efficacy.
authors.affiliation: Central Hospital Pharmacy, Escamplaan 900, 2547EX The Hague, The Netherlands. e.wilms@ahz.nl
authors.forename: E B
authors.initials: EB
authors.lastname: Wilms
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.forename: H G M
authors.initials: HG
authors.lastname: Heijerman
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017963:Azithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D013183:Sputum / Q000737:chemistry* / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin