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Pharmacokinetics of intravenous and epidural ropivacaine in the rhesus monkey
Author(s) -
Katz Jeffrey A.,
Sehlhorst Constance S.,
Thompson Gary A.,
Denson Donald D.,
Coyle Dennis,
Bridenbaugh Phillip O.
Publication year - 1993
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510140704
Subject(s) - ropivacaine , epidural administration , pharmacokinetics , bioavailability , epidural space , anesthesia , absorption (acoustics) , local anesthetic , medicine , bupivacaine , anesthetic , chemistry , pharmacology , physics , acoustics
Abstract Ropivacaine is a new long‐acting amide local anesthetic which is possibly 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 intravenous and intraarterial catheters. For the epidural studies, a PE‐10 catheter was also inserted 3 cm into the lumbar epidural space. After recovery from anesthesia, animals received ropivacaine 1 mg kg −1 intravenously 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 chromatography with NP detection. Concentration—time data following i.v. and epidural administration were fitted simultaneously. Initial parameter estimates were obtained by analyzing each route separately. Input rates and their corresponding extent of absorption were estimated using deconvolution. Mean (±SD) disposition parameters included: V ss = 1.11±0.198 1kg −1 ; CL = 0.711 ± 0.158 1 h −1 kg −1 ; t 1/2,z = 2.07 ± 0.438 h. Mean (± SD) absorption parameters included: F 1 = 0.506 ± 0.221; t 1/2, k a1= 0.060 ± 0.078 h; F 2 = 0.444 ± 0.182; t 1/2,k a2= 6.45 ± 11.09h. Ropivacaine's biphasic absorption and bioavailability are similar to those of other amide local anesthetics. The biphasic absorption may be related to partitioning into fat or regional changes in blood flow induced by the drug.