Estimated Plasma Bupivacaine Concentration After Single Dose and Eight‐Hour Continuous Intra‐Articular Infusion of Bupivacaine in Normal Dogs

Abstract

To estimate maximum plasma concentration (C(max)) and time to maximum plasma (t(max)) bupivacaine concentration after intra-articular administration of bupivacaine for single injection (SI) and injection followed by continuous infusion (CI) in normal dogs. Cross-over design with a 2-week washout period. Healthy Coon Hound dogs (n=8). Using gas chromatography/mass spectrometry, canine plasma bupivacaine concentration was measured before and after SI (1.5 mg/kg) and CI (1.5 mg/kg and 0.3 mg/kg/h). Software was used to establish plasma concentration-time curves and estimate C(max), T(max) and other pharmacokinetic variables for comparison of SI and CI. Bupivacaine plasma concentration after SI and CI best fit a 3 exponential model. For SI, mean maximum concentration (C(max), 1.33+/-0.954 microg/mL) occurred at 11.37+/-4.546 minutes. For CI, mean C(max) (1.13+/-0.509 microg/mL) occurred at 10.37+/-4.109 minutes. The area under the concentration-time curve was smaller for SI (143.59+/-118.390 microg/mL x min) than for CI (626.502+/-423.653 microg/mL x min, P=.02) and half-life was shorter for SI (61.33+/-77.706 minutes) than for CI (245.363+/-104.415 minutes, P=.01). The highest plasma bupivacaine concentration for any dog was 3.2 microg/mL for SI and 2.3 microg/mL for CI. Intra-articular bupivacaine administration results in delayed absorption from the stifle into the systemic circulation with mean C(max) below that considered toxic and no systemic drug accumulation. Intra-articular bupivacaine can be administered with small risk of reaching toxic plasma concentrations in dogs, though toxic concentrations may be approached. Caution should be exercised with multimodal bupivacaine administration because plasma drug concentration may rise higher than with single intra-articular injection.