Pharmacokinetics of ropivacaine after intraperitoneal instillation in anaesthetized dogs: a randomized clinical trial

To evaluate the pharmacokinetics of two doses of intraperitoneal ropivacaine in anaesthetized dogs.

Randomized clinical trial.

A total of 20 dogs undergoing ovariectomy/ovariohysterectomy.

Dogs were anaesthetized and randomized to be given 1 (group R1) or 3 (group R3) mg kg^-1 of ropivacaine intraperitoneally, diluted with 0.9% NaCl to a total volume of 0.8 mL kg^-1. Before abdominal wall closure, solution aliquots were instilled over the ovarian pedicles and, if applicable, the uterine stump. Venous blood was sampled 2 minutes before and 5, 10, 15, 30, 45, 60, 120 and 240 minutes after instillation. Cardiovascular signs of toxicity were noted. Plasma concentrations of free and total ropivacaine were measured using ultrahigh-performance liquid chromatography-mass spectrometry. Plasma protein binding (PPB) was determined by rapid equilibrium dialysis. Pharmacokinetic parameters were derived by a noncompartmental analysis, and the maximum total and free ropivacaine plasma concentrations (Cmax) were compared between groups using an independent samples t-test. Data are presented as mean or median (95% confidence intervals). Significance was set at p < 0.05.

One dog in R3 was excluded. Total ropivacaine Cmax values were 0.27 (0.21-0.33) and 0.67 (0.43-0.92) mg L^-1 at 15 (8.64-30.35) and 5 (1.77-8.23) minutes (Tmax) for R1 and R3, respectively, and different between groups (p = 0.005). Free ropivacaine Cmax values were 0.02 (0.02-0.03) and 0.06 (0.03-0.09) mg L^-1 at 10 (4.67-15.32) and 5 (0-19.13) minutes (Tmax) for R1 and R3, respectively, and Cmax was different between groups (p = 0.015). Median ropivacaine PPB for all dogs was 92.5% (89.7-95.2%). No signs of cardiovascular toxicity were noted.

Although R3 had a greater total and free ropivacaine Cmax than R1, Cmax remained below toxic levels in all dogs.