Open AccessPopulation Pharmacokinetics of Azithromycin in Whole Blood, Peripheral Blood Mononuclear Cells, and Polymorphonuclear Cells in Healthy Adults
Author(s) -
Sampson MR,
Dumitrescu TP,
Brouwer KLR,
Schmith VD
Publication year - 2014
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1038/psp.2013.80
Subject(s) - azithromycin , peripheral blood mononuclear cell , medicine , immunology , population , pharmacology , whole blood , volume of distribution , pharmacokinetics , blood cell , antibiotics , biology , microbiology and biotechnology , in vitro , biochemistry , environmental health
Azithromycin's extensive distribution to proinflammatory cells, including peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs), may be important to its antimicrobial and anti‐inflammatory properties. The need to simultaneously predict azithromycin concentrations in whole blood (“blood”), PBMCs, and PMNs motivated this investigation. A single‐dose study in 20 healthy adults was conducted, and nonlinear mixed effects modeling was used to simultaneously describe azithromycin concentrations in blood, PBMCs, and PMNs (simultaneous PK model). Data were well described by a four‐compartment mamillary model. Apparent central clearance and volume of distribution estimates were 67.3 l/hour and 336 l (interindividual variability of 114 and 122%, respectively). Bootstrapping and visual predictive checks showed adequate model performance. Azithromycin concentrations in blood, PBMCs, and PMNs from external studies of healthy adults and cystic fibrosis patients were within the 5th and 95th percentiles of model simulations. This novel empirical model can be used to predict azithromycin concentrations in blood, PBMCs, and PMNs with different dosing regimens. CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e103; doi: 10.1038/psp.2013.80 ; published online 5 March 2014