PHARMACOKINETICS OF 3 DOSES OF EPIDURAL ROPIVACAINE DURING HYSTERECTOMY AND COMPARISON WITH BUPIVACAINE

Purpose: Ropivacaine is a new long-acting aminoamide local anaesthetic , structurally related to bupivacaine; The clinical efficacy of 125 mg , 187.5 mg and 250 mg ropivacaine have been reported and compared with 125 mg bupivacaine for epidural analgesia during hysterectomy. In the pharmacokinetic part of this study the objectives were to 1) determin e the dose proportionality in the pharmacokinetics of epidural ropivac aine, and 2) compare the pharmacokinetic; of 125 mg ropivacaine and 12 5 mg bupivacaine. Methods: In a randomized, double-blind controlled st udy, patients received one oi four treatment regimens with ropivacaine (125, 187.5 or 250 mg) or bupivacaine (125 mg) as a 25 ml epidural bo lus administered over three minutes. Peripheral venous blood samples w ere collected over 24 hr for ropivacaine or bupivacaine quantification using gas chromatography with nitrogen sensitive detection. Pharmacok inetic variables were derived from plasma concentration-time curve dat a. Results: Fifty two women entered the study. Demographic characteris tics were similar among groups. Six patients were excluded due to inad equate sensory block or an insufficient number of plasma samples. The peak plasma concentration (C-max) of ropivacaine and the total area un der the plasma concentration-time curve (AUC) increased proportionally with the dose, Apparent plasma clearance (CL) and the terminal half-l ife (t(1/2)) were similar in the three ropivacaine groups. When compar ed with the 125 mg ropivacaine group, the bupivacaine group had a long er terminal half life (P < 0.05). Conclusions: Epidural ropivacaine di splays lose-proportional pharmacokinetic behaviour for doses of 125 mg to 250 mg, Ropivacaine has a shorter terminal half-life than bupivaca ine.