The disposition of florfenicol after single intravenous and intramuscular doses of 20 mg of florfenicol/kg of body weight (b.w.) to feeder calves was investigated. Serum florfenicol concentrations were determined by a sensitive high performance liquid chromatographic method with a limit of quantitation of 0.025 microgram/ml. The extent of serum protein binding of florfenicol was only 13.2% at a serum florfenicol concentration of 3.0 micrograms/ml. Serum concentration-time data after intravenous administration were best described by a triexponential equation. Total body clearance and steady state volume of distribution were 3.75 ml/min/kg b.w. and 761 ml/kg b.w., respectively. The terminal half-life after intravenous administration was 159 min. The absolute systemic availability after intramuscular administration was 78.5% (range: 59.3-106%) and the harmonic mean of the terminal half-life was 1098 minutes, indicating slow release of the florfenicol from the formulation at the intramuscular injection site.

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. Patients with MS typically present with visual, motor, and sensory deficits. However, an additional complication of MS in large subset of patients is neuropathic pain. To study the underlying immune-mediated pathophysiology of pain in MS we employed the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis (EAE) model in mice. Since sensory neurons are crucial for nociceptive transduction, we investigated the effect of this disease on sensory neurons of the lumbar dorsal root ganglia (DRG). Here, we report the disease was associated with activation of the complement system and the NLRP3 inflammasome in the DRG. We further observe a transient increase in the number of complement component 5a receptor 1-positive (C5aR1+) immune cells, CD4+ T-cells, and Iba1+ macrophages in the DRG. The absence of any significant change in the levels of mRNA for myelin proteins in the DRG and the sciatic nerve suggests that demyelination in the PNS is not a trigger for the immune response in the DRG. However, we did observe an induction of activating transcription factor 3 (ATF3) at disease onset and chronic disruption of cytoskeletal proteins in the DRG demonstrating neuronal injury in the PNS in response to the disease. Electrophysiological analysis revealed the emergence of hyperexcitability in medium-to-large (≥26 µm) diameter neurons, especially at the onset of MOG-EAE signs. These results provide conclusive evidence of immune activation, neuronal injury, and peripheral sensitization in MOG-EAE, a model classically considered to be centrally mediated.

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Florfenicol administered SC (1 dose) or IM (2 doses 48 hours apart) was effective for treatment of calves with naturally occurring IBK.