Ac. Santos et al., COMPARATIVE PHARMACOKINETICS OF ROPIVACAINE AND BUPIVACAINE IN NONPREGNANT AND PREGNANT EWES, Anesthesia and analgesia, 85(1), 1997, pp. 87-93
We determined the pharmacokinetics and protein binding of ropivacaine
and bupivacaine after intravenous administration to nonpregnant and pr
egnant sheep. All animals were in good condition throughout the study.
The highest mean total serum drug concentrations were found at the en
d of infusion. For both drugs, pregnancy was associated with lower vol
umes of distribution during the terminal phase of drug elimination (V-
d beta) and steady state (V-dss), as well as with a lower total body c
learance (CL). The relationship between V-d beta and CL was such that
the elimination half-life (T 1/2(beta)) was not altered. There were al
so differences the two drugs. In all animals, the distribution half-li
fe (T 1/2(alpha) ), T 1/2(beta), volume of central compartment (V-c),
V-d beta' V-dss' and mean residence times (MRT) were greater and CL lo
wer for bupivacaine than ropivacaine. For both drugs, protein binding
was concentration-dependent and greater in pregnant ewes. In conclusio
n, the pharmacokinetics of ropivacaine and bupivacaine are altered by
ovine pregnancy in a similar way. If these data are applicable to huma
ns, an unintended intravascular injection of either drug could be expe
cted to result in higher total serum concentrations in the pregnant th
an in the nonpregnant patient, but drug levels would decline at simila
r rates in both groups of individuals. However, differences between th
e two drugs, particularly in T 1/2(beta) and MRT, may make ropivacaine
preferable for use in obstetric anesthesia.