Pharmacokinetics, safety, and biologic effects of azithromycin in extremely preterm infants at risk for ureaplasma colonization and bronchopulmonary dysplasia

J Clin Pharmacol. 2011 Sep;51(9):1264-75. doi: 10.1177/0091270010382021. Epub 2010 Nov 23.


Ureaplasma spp. respiratory tract colonization is a significant risk factor for bronchopulmonary dysplasia (BPD), a chronic lung disorder in preterm infants. As an initial step preparatory to future clinical trials to evaluate the clinical efficacy of azithromycin to prevent BPD, the authors characterized the pharmacokinetics, safety, and biological effects of a single intravenous dose of azithromycin (10 mg/kg) in preterm neonates (n = 12) 24 to 28 weeks gestation at risk for Ureaplasma infection and BPD. A 2-compartment structural model with the clearance and volume of peripheral compartment (V2) allometrically scaled on body weight (WT) best described the pharmacokinetics of azithromycin in preterm neonates. The estimated parameters were clearance [0.18 L/h × WT(kg)(0.75)], intercompartmental clearance [1.0 L/h], volume of distribution of central compartment [0.93 L], and V2 [14.2 L × WT(kg)]. There were no serious adverse events attributed to azithromycin. A single dose of azithromycin did not suppress inflammatory cytokines or myeloperoxidase activity in tracheal aspirates. These results demonstrated the safety of azithromycin and developed a pharmacokinetic model that is useful for future simulation-based clinical trials for eradicating Ureaplasma and preventing BPD in preterm neonates.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Azithromycin / adverse effects
  • Azithromycin / pharmacokinetics*
  • Azithromycin / therapeutic use
  • Bronchopulmonary Dysplasia / drug therapy
  • Bronchopulmonary Dysplasia / metabolism*
  • Female
  • Humans
  • Infant, Extremely Low Birth Weight / metabolism*
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy
  • Infant, Premature, Diseases / metabolism*
  • Male
  • Respiration, Artificial / adverse effects
  • Ureaplasma / drug effects
  • Ureaplasma / isolation & purification*
  • Ureaplasma Infections / diagnosis
  • Ureaplasma Infections / drug therapy*
  • Ureaplasma Infections / metabolism*


  • Azithromycin