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Pharmacokinetics and sputum penetration of azithromycin during once weekly dosing in cystic fibrosis patients. 2008

E B Wilms, and D J Touw, and H G M Heijerman
Central Hospital Pharmacy, Escamplaan 900, 2547EX The Hague, The Netherlands. e.wilms@ahz.nl

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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D003550 Cystic Fibrosis An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION. Mucoviscidosis,Cystic Fibrosis of Pancreas,Fibrocystic Disease of Pancreas,Pancreatic Cystic Fibrosis,Pulmonary Cystic Fibrosis,Cystic Fibrosis, Pancreatic,Cystic Fibrosis, Pulmonary,Fibrosis, Cystic,Pancreas Fibrocystic Disease,Pancreas Fibrocystic Diseases
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D013183 Sputum Material coughed up from the lungs and expectorated via the mouth. It contains MUCUS, cellular debris, and microorganisms. It may also contain blood or pus. Sputum, Induced,Induced Sputum,Induced Sputums,Sputums,Sputums, Induced

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