Bupivacaine and liposomal bupivacaine do not produce prolonged perineural anesthesia in a lameness model and are detectable beyond clinical effect in conditioned Thoroughbreds.

Abstract

To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossover pharmacokinetic/pharmacodynamic trials (n = 12/group). Data were analyzed using a paired t test or Wilcoxon signed-rank test, P < .05. The 133-mg/nerve dose of LB eliminated lameness in 3 of 3 horses in the dose-response trial, and lameness returned at 6, 36, and 72 hours. In the pharmacokinetic/pharmacodynamic trials, time to return of lameness greater than or equal to starting lameness was longer for LB compared to BH on subjective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 4 to 12 hours) and objective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 2 to 6 hours) evaluations. The terminal half-life was not different between formulations (LB, 17.8 hours ± 10.1; BH, 12.4 hours ± 6.3); however, LB had increased area under the concentration-versus-time curve from time 0 to infinity (LB, 388 ng·h/mL ± 117; BH, 63 ng·h/mL ± 18) and mean residence time (LB, 17.6 hours ± 2.4; BH, 3.9 hours ± 1.6). Liposomal bupivacaine analgesia duration was greater than BH, but the median time until lameness returned was only 12 hours. Bupivacaine is quantifiable in serum and urine beyond loss of clinical effect. A single, high-dose injection of LB is not effective for providing perineural analgesia over several days. Bupivacaine is detectable after the effect of the drug has worn off.