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Lipophilicity affects the pharmacokinetics and toxicity of local anaesthetic agents administered by caudal block
Author(s) -
NavaOcampo Alejandro A,
BelloRamírez Angélica M
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.03961.x
Subject(s) - ropivacaine , toxicity , pharmacokinetics , local anaesthetic , clearance , anesthesia , medicine , plasma concentration , pharmacology , chemistry , urology
Summary 1. Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2. In the present study, we examined the relationship between the octanol–water partition coefficient (log P oct ) and the time to reach the maximum plasma drug concentration (t max ) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log P oct and the toxicity of these local anaesthetic agents in experimental models. The t max and toxicity data were obtained from the literature. 3. Ropivacaine, with a log P oct of 2.9, exhibited a t max of 61.6 min. The t max of lignocaine, with a log P oct of 2.4, and bupivacaine, with a log P oct of with 3.4, were approximately 50% shorter than ropivacaine. At log P oct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log P oct and the convulsive effect in dogs was similar to the relationship between log P oct and the lethal dose in sheep. 4. With local anaesthetic agents, it appears that the relationship between log P oct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log P oct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log P oct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system.