Pharmacokinetics of azithromycin in foals after i.v. and oral dose and disposition into phagocytes

Authors

  • J. L. DAVIS,

    1. Department of Clinical Sciences (Davis, Gardner, Jones, Schwabenton), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA,
    Search for more papers by this author
  • S. Y. GARDNER,

    1. Department of Clinical Sciences (Davis, Gardner, Jones, Schwabenton), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA,
    Search for more papers by this author
  • S. L. JONES,

    1. Department of Clinical Sciences (Davis, Gardner, Jones, Schwabenton), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA,
    Search for more papers by this author
  • B. A. SCHWABENTON,

    1. Department of Clinical Sciences (Davis, Gardner, Jones, Schwabenton), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA,
    Search for more papers by this author
  • M. G. PAPICH

    1. Department of Anatomy, Physiological Sciences and Radiology (Papich), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA
    Search for more papers by this author

Sarah Y. Gardner Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606. E-mail: Sarah Gardner@ncsu.edu

Abstract

The properties of azithromycin suggest that it may be an alternative to erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate this possibility, the disposition of azithromycin in plasma, polymorphonuclear leukocytes (PMN), and alveolar cells was examined after a single administration in foals. Azithromycin suspension was administered orally (p.o.) at a dose of 10 mg/kg to five healthy 2–3-month-old foals. Two weeks later, azithromycin for injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to the same foals. Plasma samples were collected after p.o. and i.v. administration. Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were collected after p.o. administration. Azithromycin concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC) with coulometric electrochemical detection. Azithromycin p.o. absorption was variable with a mean systemic availability of 39% (±20%). The plasma half-life was 16 and 18.3 h after i.v. and p.o. administration, respectively. Azithromycin had a very large volume of distribution (Vd) of 11.6 L/kg [Vd(ss)] and 12.4 L/kg [Vd(area)]. The large Vd can be attributed to high tissue and intracellular concentrations, exhibited by the high concentration of azithromycin in PMN and alveolar cells. The PMN half-life was 49.2 h. Dosage of 10 mg/kg of azithromycin p.o. once daily for foals with R. equi pneumonia is recommended for further study.

Ancillary