Comparative Pharmacokinetics of Bupivacaine and Ropivacaine, a New Amide Local Anesthetic

ARTHUR GR, FELDMAN HS, COVINO BJ. Comparative pharmacokinetics of bupivacaine and ropivacaine, a new amide local anesthetic. Anesth Analg 1988;67:1053-8. The pharmacokinetics of ropivacaine, a new amide local anesthetic, and bupivacaine were determined in dogs after IV and epidural administration. After 15-minute IV infusions of 3.0 mg/kg ropivacaine (n = 6) and 3.4 mg/kg bupivacaine (n = 4), the maximum arterial concentrations (Cmax) of ropivacaine averaged 2.41 ± 0.52 μg/ml compared with 3.35 ± 0.16 μg/ml of bupivacaine. The elimination half life (t1/2β) of ropivacaine (25.9 ± 1.7 min) was significantly shorter than for bupivacaine (39.1 ± 13.3 min) after IV infusion. This was reflected by mean clearance values (Cl) for ropivacaine of 41.1 ± 8.2 ml.min−1.kg−1 compared with 32.3 ± 4.8 ml.min−1.kg−1 for bupivacaine, although the difference was not statistically significant. After epidural injections (ropivacaine n = 6; bupivacaine n = 5), a dose-related increase increase in Cmax was observed with both drugs. Although Cmax tended to be higher for ropivacaine, a significant difference was only attained when comparing Cmax after administration of 0.25% plain solutions of both agents. The addition of epinephrine did not consistently decrease the Cmax of either agent. The apparent t1/2β of both agents was significantly longer after epidural administration than after IV infusion. No differences existed between t1/2β values for ropivacaine and bupivacaine after epidural administration. Total body clearance of both agents tended to be lower after epidural administration, particularly when epinephrine-containing solutions were employed. Little difference existed between the two drugs when equivalent solutions were administered. The results of this pharmacokinetic study indicate that after IV infusion of bupivacaine and ropivacaine, concentrations of ropivacaine decrease more rapidly than bupivacaine during the elimination phase. This may result in a greater margin of safety for the new agent. However, after epidural administration, the pharmacokinetic profiles of the two drugs were quite similar.