Florfenicol Pharmacokinetics in Healthy Adult Alpacas, Evaluating Two Commercially Available Drug Formulations.

D Bedenice1, MG Papich2, K Thane1, K Holmes1. 1Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA. 2North Carolina State University, Raleigh, NC.

Single-dose florfenicol pharmacokinetics were compared using 2 commercially available drug formulations (Nuflor®, NuflorGold®, Schering-Plough) in 6 healthy adult alpacas, administered at 40 mg/kg subcutaneously (s.c.) using a randomized, cross-over design. Subsequently, each formulation of florfenicol was injected s.c. every 48 hours for 10 doses (40 mg/kg) to evaluate long-term effects. Clinical parameters were monitored daily in addition to weekly hematological analyses. Plasma drug concentrations were obtained via high-performance liquid chromatography at 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, 36, 48, 60, 72, 96 and 120 h post-injection for single-dose studies, and at 0, 2, 4, and 8 h after the last dose for multi-dose studies. The florfenicol plasma concentrations vs. time plots were analyzed using a non-compartmental analysis (Nuflor®) or 2 compartment model (NuflorGold®), and commercial software (Phoenix WinNonlin 6.0). All data are presented as mean ± standard deviation; hematological parameters were compared between time points using repeated measures ANOVA and paired samples t-test post hoc.

Maximum plasma florfenicol concentrations (Cmax) were achieved rapidly following single dose injections. Comparative pharmacokinetic parameters are listed in Table 1 below:

Maximum plasma concentrations of 4.48±1.28 and 7.62±1.65 µg/mL were achieved at steady state for Nuflor® and NuflorGold®, respectively, after 10 doses. The following hematological parameters decreased significantly between weeks 0 and 3, following repeated Nuflor® injection: total protein [TP] (6.38 vs. 5.61 g/dL, P less than 0.0001), globulin (2.76 vs. 2.16g/dL, P less than 0.0003), albumin (3.61 vs. 3.48g/dL, P=0.0038), white blood cell count [WBC] (11.89 vs. 9.66×10^3/μL, P less than 0.044), and hematocrit (27.25 vs. 24.88%, P less than 0.0349). Significant clinical illness was observed in one alpaca. Similarly, the following parameters significantly decreased after 10 doses of 40mg/kg NuflorGold®: TP (6.65 vs. 5.98 g/dL, P=0.009), globulin (2.82 vs. 2.28g/dL, P=0.004), WBC (14.75 vs. 9.27×10^3/μL, P=0.001). No clinical illness was observed in the latter group.

In conclusion, both Nuflor® and NuflorGold® may be erratically absorbed following s.c. administration in adult alpacas, based on the observed variability in most measured pharmacokinetic parameters. Plasma concentrations of NuflorGold® reached higher therapeutic concentrations, yet were associated with fewer systemic complications following long term use.

This work has been published in J Vet Pharmacol Ther 2012, 35(4) 382-388.