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Pharmacokinetic Profile in Dogs

NOCITA® (bupivacaine liposome injectable suspension) is administered as a single treatment by tissue infiltration during surgical closure into the tissues to control post-operative pain in cranial cruciate ligament (CCL) surgery in dogs. The pharmacokinetic characterization associated with bupivacaine after subcutaneous NOCITA or bupivacaine HCl solution was administered to beagle dogs is provided in Table 3.21

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Absorption in Dogs

Following single subcutaneous doses of 9 mg/kg and 18 mg/kg NOCITA, the median time to reach Cmax was rapid (0.5 hr), but it was delayed significantly at a high dose of 30 mg/kg (60 hr).21 Following equivalent doses (9 mg/kg) of NOCITA and bupivacaine HCl solution, the mean bupivacaine AUC(0-72) and Tmax were comparable. However, due to the slow release mechanism of NOCITA, the mean Cmax and T1/2 on day 1 were approximately 3-fold lower and 3.5-fold higher, respectively, compared with those of bupivacaine HCl. Following an increase in dose of NOCITA, the bupivacaine pharmacokinetics were nonlinear, with high variability in exposure parameters. Both Cmax and AUC(0-72) increased with dose, but the increases were less than dose proportional. Furthermore, the nonlinear bupivacaine pharmacokinetics was made evident by an increase in the terminal-phase half-life with the increase in dose.21 Of note, NOCITA can result in measurable systemic bupivacaine in plasma for up to 96 hours, but the systemic plasma levels do not necessarily correlate with local efficacy.23

21. NOCITA® [package insert]. Leawood, KS: Aratana Therapeutics, Inc.; 2018.

23. Richard BM, Ott LR, Haan D, et al. The safety and tolerability evaluation of DepoFoam bupivacaine (bupivacaine extended-release liposome injection) administered by incision wound infiltration in rabbits and dogs. Expert Opin Investig Drugs. 2011;20(10):1327-1341.