PHARMACOKINETICS OF INTRAVENOUS AND EPIDURAL ROPIVACAINE IN THE RHESUS-MONKEY

Ropivacaine is a new long-acting amide local anesthetic which is possi bly less cardiotoxic than bupivacaine. The absorption and disposition of ropivacaine were characterized in six rhesus monkeys in an open two -way crossover study following intravenous and epidural administration . For these studies, animals were anesthetized for placement of intrav enous and intraarterial catheters. For the epidural studies, a PE-10 c atheter was also inserted 3 cm into the lumbar epidural space. After r ecovery from anesthesia, animals received ropivacaine 1 mg kg-1 intrav enously over 1 min or 10 mg of ropivacaine epidurally (two 1 ml doses of 0.5%, 5 min apart), and arterial blood samples were obtained over 5 h. Serum ropivacaine concentrations were determined by gas chromatogr aphy with NP detection. Concentration-time data following i.v. and epi dural administration were fitted simultaneously. Initial parameter est imates were obtained by analyzing each route separately. Input rates a nd their corresponding extent of absorption were estimated using decon volution. Mean (+/- SD) disposition parameters included: V(ss) = 1.11 +/- 0.198 1 kg-1; CL = 0.711 +/- 0.158 1 h-1 kg-1; t1/2,z = 2.07 +/- 0 .438 h. Mean (+/- SD) absorption parameters included: F1 = 0.506 +/- 0 .221; t1/2,ka1 = 0.060 +/- 0.078 h; F2 = 0.444 +/- 0.182; t1/2,ka2 = 6 .45 +/- 11.09 h. Ropivacaine's biphasic absorption and bioavailability are similar to those of other amide local anesthetics. The biphasic a bsorption may be related to partitioning into fat or regional changes in blood flow induced by the drug.