COMPARATIVE PHARMACOKINETICS OF ROPIVACAINE AND BUPIVACAINE IN NONPREGNANT AND PREGNANT EWES

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.