Open AccessToxicity of Bupivacaine and Ropivacaine in Relation to Free Plasma Concentrations in Pregnant Rats: A Comparative Study
Author(s) -
Danielsson Bengt R. G.,
Danielson M. Kiki,
Böö Éva Lindström,
Arvidsson Torbjörn,
Halldin Magnus M.
Publication year - 1997
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1111/j.1600-0773.1997.tb00037.x
Subject(s) - ropivacaine , bupivacaine , medicine , toxicity , anesthesia , litter , local anesthetic , offspring , pregnancy , pharmacology , biology , genetics , agronomy
The relationship between free drug concentration and toxicity of bupivacaine and ropivacaine, a new local anaesthetic agent, was studied in a pregnant rat model. The compounds were given subcutaneously to rats in late pregnancy. Dose levels (bupivacaine 5.5 to 24 mg/kg and ropivacaine 5.3 to 26 mg/kg) were selected based upon the proposed human dosage and the known pharmacological activity of the compounds. Chewing, spasm, dyspnoea, drowsiness, salivation and convulsions were observed in a dose‐dependent manner in the animals given 14 to 24 mg/kg of bupivacaine, while only a few animals receiving 26 mg/kg of ropivacaine showed less severe symptoms. Deaths from clonic convulsions were occasionally seen in animals receiving 14 mg/kg or more of bupivacaine. No animals receiving ropivacaine died. No effects on litter size, offspring loss or weight of the offspring at birth were observed with one exception. After 24 mg/kg of bupivacaine an increased postnatal loss of the off springs were noticed, most likely due to impaired maternal care. Protein binding, at expected C max , were significantly lower for ropivacaine (around 49%) compared with bupivacaine (around 69%) at dose levels. The results suggest an increased safety margin before onset of toxic side effects after treatment with ropivacaine, compared to bupivacaine, in pregnant rase.