PHARMACOKINETICS OF ROPIVACAINE AND BUPIVACAINE DURING 21 HOURS OF CONTINUOUS EPIDURAL INFUSION IN HEALTHY MALE-VOLUNTEERS

The aim of the present study was to evaluate the pharmacokinetics of r opivacaine and to compare the results with those of bupivacaine during prolonged epidural infusion. Ropivacaine 1, 2, or 3 mg/mL (0.1%, 0.2% , or 0.3%), bupivacaine 2.5 mg/mL (0.25%), or placebo (sodium chloride 0.9%) was given randomly and in a double-blind manner to five paralle l treatment groups (37 healthy volunteers) as a continuous epidural in fusion for 21 h. A 10-mL epidural bolus dose was first given, and the epidural infusion was started immediately afterward. The subjects rece ived 10 mL/h corresponding to infusion rates of 10, 20, or 30 mg/h rop ivacaine and 25 mg/h bupivacaine, respectively. Peripheral blood sampl es for measurements of ropivacaine or bupivacaine were taken during a 25-h period. The total plasma concentration increased continuously but seemed to reach a plateau (C-5-10h) after approximately 5 h infusion, remaining fairly constant up to approximately 10 h after the start of administration. The C-5-10h values were proportional to the dose of r opivacaine and were estimated as 0.3, 0.6, and 0.9 mg/L, and for bupiv acaine as 0.7 mg/L. During the subsequent infusion the plasma concentr ation increased, with maximum plasma levels at the end of the infusion and with corresponding values of 0.4, 0.9, 1.2, and 0.9 mg/L. The hig hest individual plasma concentration was 1.7 mg/L (20 mg/h), and no pa tient showed signs of toxic systemic plasma levels. The free concentra tions also increased continuously during the infusion. The free fracti on was independent of the dose (6.1% for ropivacaine and 4.8% for bupi vacaine). The pharmacokinetics of ropivacaine was linear in the studie d range of infusion rates (up to total plasma concentrations of approx imately 2 mg/L).