The Pharmacokinetics of Tulathromycin Following Subcutaneous Administration in Rhesus Macaques (Macaca mulatta)
Campylobacter jejuni is a pathogenic bacterium commonly associated with enteritis and diarrhea in rhesus macaques (Macaca mulatta). The standard therapy at the California National Primate Research Center is oral azithromycin, a second-generation macrolide, given daily for 5 d. Oral treatment administration can be difficult with some animals. Poor oral compliance for antibiotics can result in treatment failure and potentially select for antibiotic resistance. Tulathromycin, a newer-generation macrolide, may offer an injectable alternative to azithromycin. The aim of the current study is to quantify the pharmacokinetics of tulathromycin in plasma in rhesus macaques. Six rhesus macaques were each given a single 2.5 mg/kg dose SC of tulathromycin, and serial blood samples were collected at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2, 4, 8, 12, 24, 48, 72, 96, 120, and 168 h, to quantify the concentration of tulathromycin in plasma over time. Results show that Cmax = 1,280 ± 395 ng/mL, Tmax = 1.25 ± 0.5 h, t1/2 = 77.2 ± 15.4 h, and AUC0-168 = 6,557.4 ± 875.4 h·ng/mL. There are no published Clinical and Laboratory Sciences Institute breakpoints for tulathromycin against C. jejuni, but based on an independently established minimum inhibitory concentration of 500 ng/mL, these data suggest that 2.5 mg/kg tulathromycin can be given subcutaneously to achieve potential therapeutic levels in rhesus macaques, possibly providing an alternative to oral azithromycin.
(A) Mean with SD bars showing concentration in plasma over time after subcutaneous injection of a single dose of tulathromycin (2.5 mg/kg) to 6 rhesus macaques (Macaca mulatta). Tulathromycin administration was designated as time 0. Peak plasma concentration (ng/mL; mean ± SD) was 1,280 ± 395. (B) Mean with SD bars showing tulathromycin concentrations in plasma over just the first 12 h. The red dashed lines on both plots represent the MIC of 500 ng/mL.
Nonparametric superposition models demonstrating predicted plasma concentrations. The dark line is mean, and the shaded regions represent 95% CI of the mean. (A) Following daily administration of tulathromycin at 2.5 mg/kg SC. (B) Following every other day administration of tulathromycin at 2.5 mg/kg SC. The red dashed lines on both plots represent the MIC of 500 ng/mL.
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