title: Pharmacokinetics of ropivacaine and bupivacaine during 21 hours of continuous epidural infusion in healthy male volunteers.
abstract: 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)
mesh_terms: 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
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D010919:Placebos; D000077212:Ropivacaine; D002045:Bupivacaine