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Pharmacokinetics of Ropivacaine in Nonpregnant and Pregnant Ewes

Received from the Departments of Anesthesiology and of Obstetrics and Gynecology, School of Medicine, State University of New York—Stony Brook, Stony Brook, New York; the College of Physicians & Surgeons of Columbia University, New York, New York; the Department of Aresthesiology, State University of New York—Downstate Medical Center, Brooklyn, New York; and the Department of Anesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.

Abstract

The pharmacokinetics of ropivacaine were studied in chronically instrumented nonpregnant and pregnant ewes. On the day of study, the urinary bladder was catheterized. Ropivacaine (2.5 or 3.0 mg/kg) was administered by intravenous infusion over 2 or 4 min. Serial samples of arterial blood and urine were collected over 5 h, and drug concentrations were determined using a gas chromatographic technique. Total clearance of ropivacaine was lower in the pregnant animals (21.6 ± 4.5 mL·min^–1 ·kg^–1) compared with the nonpregnant animals (45.1 ± 6.7 mL·min^–1 ·kg^–1). There was a tendency toward a decrease in the volume of distribution during the terminal exponential phase of drug elimination of 2.03 ± 0.36 L/kg in the pregnant and 4.32 ± 1.03 L/kg in the nonpregnant sheep. Thus the difference in the elimination half-life was only minimal: 74.7 ± 10.7 min in the pregnant and 64.4 ± 7.4 min in the nonpregnant animals. It is concluded that ovine pregnancy is accompanied by changes in the pharmacoki- netics of ropivacaine. Inadvertent intravenous injections of similar drug doses to pregnant and nonpregnant women might result in higher plasma concentrations of ropivacaine in the former. However, the rate of decline in plasma levels of the drug would be similar in both.

Key Words: ANESTHETICS, LOCAL—ropivacaine • PHARMACOKINETICS, ROPIVACAINE • PREGNANCY, PHARMACOKINETICS—ropivacaine • ANESTHESIA, OBSTETRICAL