Pharmacodynamics and Pharmacokinetics of Epidural Ropivacaine in Humans

Abstract

The purpose of this study was to characterize the pharmacodynamics and pharmacokinetics of three concentrations of the new long-acting amide local anesthetic, ropivacaine, given epidurally in 15 physical status ASA I or II patients for elective, lower-extremity orthopedic procedures using a nonrandomized open-label design. Three groups of five patients each received either 0.57%, 0.75%, or 1.0% ropivacaine. Upper and lower levels of analgesia to pinprick were determined at frequent intervals until normal sensation had completely returned. Motor blockade ums assessed by use of a modified Bromage scale after each determination of level of analgesia. Fifteen venous blood samples were collected over 12 h after ropivacaine injection. Pharmacokinetic parameters were derived using serum concentration-time data. No significant differences were found between the three groups in terms of onset or recovery of motor and sensory blockade. Median maximum thoracic levels of analgesia achieved were 8, 6, and 5 for the 0.5%, 0.75%, and 1.0% groups, respectively, and occurred at 29 ± 11, 37 ± 23, and 30 ± 9 min. Respective times to two-segment regression were 2.8 ± 1.0, 3.0 ± 0.5, and 2.9 ± 0.6 h. Total durations of sensory blockade were 5.4 ± 0.7, 6.5 ± 0.4, and 6.8 ± 0.8 h, respectively. No statistically significant differences were noted between the three groups in term of clearance (CL). The mean residence time (MRT) was significantly longer for the 0.5% group when compared with the 1% group. The peak concentration (Cmax) for the 0.5% group was found to be significantly lower than for either the 0.75% or 1% groups. Mean (± SD) values of the pharmacokinetic parmeters for the 0.5%, 0.75%, and 1.0% groups were, respectively, MRT: 9.9 ± 3.6, 7.5 ± 2.6, and 4.5 ± 0.8 h; CL: 0.35 ± 0.21, 0.34 ± 0.24, and 0.52 ± 0.11 L·kg−1·h−1; Cmax: 0.53 ± 0.19, 1.07 ± 0.57, and 1.53 ± 0.60 μg/mL; and tmax: 1.6 ± 1.4, 0.66 ± 0.19, and 0.65 ± 0.16 h. Pharmacokinetic and pharmacodynamic characteristics of epidural ropivacaine are similar to those of epidural bupivacaine in humans.