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

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 (V(d)) of 11.6 L/kg [V(d(ss))] and 12.4 L/kg [V(d(area))]. The large V(d) 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.

In Vitro Susceptibilities ofRhodococcus equiand Other Common Equine Pathogens to Azithromycin, Clarithromycin, and 20 Other Antimicrobials

“…In the present study, CLR was at least as active as ERY against R. equi in vitro, whereas AZI was eightfold less active. MIC 90 s of CLR and AZI against R. equi in the present study were considerably below achievable concentrations of these drugs in serum, pulmonary epithelial lining fluid, or bronchoalveolar cells following oral administration to foals (6,14,15). In contrast to the macrolides evaluated in the present study (ERY, CLR, and AZM), tilmicosin, a veterinary macrolide, has poor in vitro activity against R. equi, with MIC 90 s of Ͼ32 g/ml (4).…”

“…In people, the incidence and the severity of side effects for these drugs are also considerably decreased from those for ERY (25). The pharmacokinetics of these antimicrobial agents in foals have recently been investigated (6,14,15). However, the paucity of in vitro susceptibility studies precludes the rational use of these antimicrobial agents for the treatment of R. equi infections in foals.…”

The efficacy of a combination of azithromycin and toltrazuril for the treatment of calves naturally infected with cryptosporidiosis: a randomised, double-blind, placebo-controlled comparative clinical trial

“…Azithromycin and toltrazuril have different mechanisms of action (Baba et al 1998;Gottstein et al 2001;Davis et al 2002;Dirikolu et al 2009). Thus, we also tried a combination of azithromycin and toltrazuril as a treatment option.…”

“…Studies conducted in numerous species have, taken together, demonstrated that azithromycin has good oral bioavailability and exhibits an extensive tissue distribution with very slow elimination; thus, it exerts a prolonged anti-bacterial effect at the site of action. Furthermore, azithromycin has an augmented stability at acid pH, and reaches a high tissue concentration due to direct uptake and delivery via phagocytes (Davis et al 2002).…”

Comparative Veterinary Pharmacokinetics

“…This phenomenon is called "ion trapping". Thus, lipophilic, alkaline drugs, like erythromycin, azythromycin, clarythromycin, clindamycin, minocycline or florfenicol have important clinical role (Davis et al, 2002, Yamazaki et al, 2008 in the treatment of infections caused by intracellular pathogens (Mycoplasma spp., Chlamydia spp., Rhodococcus equi etc.) or mastitis.…”