In the context of a development program to obtain the market authorization of
injectable gamithromycin 15% w/v
solution (Zactran®, Boehringer Ingelheim) for use in sheep against footrot, the pharmacokinetic profile of
gamithromycin was established and the safety and efficacy of the treatment were confirmed in a multicenter field study in Europe. The basic pharmacokinetic parameters established in healthy young Merino sheep administered
gamithromycin at 6 mg/kg
body weight based on the analysis of plasma samples which were collected in intervals up to 12 days after
subcutaneous injection were: area under the curve until last quantifiable concentration, 8.88 ± 2.33 μg*h/mL; maximum plasma concentration, 448 ± 180 ng/mL; terminal half-life, 42.5 ± 5.25 h. The safety and clinical efficacy against footrot of
gamithromycin 15% w/v
solution were evaluated in comparison to
tilmicosin 30% w/v
solution (Micotil®, Elanco) treatment in 364 sheep of various breeds, sex and age from commercial farms in the United Kingdom (2 sites), Germany (3 sites) and France (1 site). Animals were enrolled based on lesions characteristic of footrot and lameness associated with the presence of footrot-related bacterial pathogens and were randomly allocated and treated in a 1:1 ratio with a single subcutaneous dose of
gamithromycin or
tilmicosin at label dosage (6 or 10 mg/kg
body weight, respectively). Lameness and footrot lesions were evaluated at five and 21 days
after treatment; the injection site in all animals was examined the day
after treatment and followed up daily in the animals with
injection site reaction until complete
injection site reaction resolution. Samples of 310 and 120 animals tested positive for Dichelobacter nodosus and Fusobacterium necrophorum, respectively, at inclusion, and data of 359 animals were included into the combined analyses (5 animals excluded for unintentional overdosing [1], lack of follow-up [1], concurrent
antibiotic medication for non-footrot conditions [3]). Lameness scores at 21 days
after treatment demonstrated a significantly (p = 0.0396) better success for the
gamithromycin treatment compared to the
tilmicosin treatment (97.8% vs. 93.3%). Post-dosing footrot lesion scores followed similar trends of rapid and marked decrease (improvement) for both treatments with similar (p = 0.127) treatment success for the
gamithromycin and
tilmicosin treatments (97.8% and 96.0%, respectively). Both treatments were safe;
injection site reactions noted in 19
gamithromycin- and 25
tilmicosin-treated animals resolved within five days or six days of treatment, respectively.
Gamithromycin 15% w/v
solution administered once to sheep by
subcutaneous injection at 6 mg/kg
body weight demonstrated a pharmacokinetic profile similar to that reported previously in sheep and cattle and was confirmed to be a safe and efficacious treatment for naturally occurring ovine footrot in a multicenter clinical field study conducted in Europe.