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 ropivacaine 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 parallel treatment groups (37 healthy volunteers) as a continuous epidural infusion for 21 h. A 10-mL epidural bolus dose was first given, and the epidural infusion was started immediately afterward. The subjects received 10 mL/h corresponding to infusion rates of 10, 20, or 30 mg/h ropivacaine and 25 mg/h bupivacaine, respectively. Peripheral blood samples 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 (C5-10h) after approximately 5 h infusion, remaining fairly constant up to approximately 10 h after the start of administration. The C5-10h values were proportional to the dose of ropivacaine and were estimated as 0.3, 0.6, and 0.9 mg/L, and for bupivacaine as 0.7 mg/L. During the subsequent infusion the plasma concentration 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 highest individual plasma concentration was 1.7 mg/L (20 mg/h), and no patient showed signs of toxic systemic plasma levels. The free concentrations also increased continuously during the infusion. The free fraction was independent of the dose (6.1% for ropivacaine and 4.8% for bupivacaine).(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D007268:Injections, Epidural; D008297:Male; D009407:Nerve Block; D010919:Placebos; D000077212:Ropivacaine; D013997:Time Factors
D000577:Amides; D000779:Anesthetics, Local; D010919:Placebos; D000077212:Ropivacaine; D002045:Bupivacaine