Pharmacokinetics of Lidocaine in Nonpregnant and Pregnant Ewes

Abstract

The pharmacokinetics of lidocaine were studied in nonpregnant and pregnant ewes. The maternal femoral vessels were cannulated and, on the day of study, the urinary bladder was catheterized. Lidocaine HCl, 4-5 mg/kg, was administered by IV injection over 60 seconds. Serial samples of arterial blood and urine were collected over 4 hours, and drug concentrations were determined using a gas chromatographic technique. The volume of the central compartment was greater in pregnant than in nonpregnant ewes (1.51 +/- 0.20 vs. 0.96 +/- 0.16 L/kg) as was the volume of distribution at steady state (Vdss): 3.24 +/- 0.40 vs. 1.88 +/- 0.32 L/kg. The volume of distribution during the terminal exponential phase of drug elimination (Vd beta) and total clearance of lidocaine (Cl) were also higher in pregnant animals: 4.17 +/- 0.50 L/kg and 99.6 +/- 8.5 ml.min-1.kg-1, respectively; compared to 2.46 +/- 0.48 L/kg and 44.1 +/- 6.5 ml.min-1.kg-1, in nonpregnant ewes. However, the balance between these changes in Vd beta and Cl did not result in a significant difference in the elimination half-life of lidocaine (38.1 +/- 2.1 minutes in nonpregnant and 31.9 +/- 3.0 minutes in pregnant ewes). If these data are applicable to humans, the risk of drug accumulation after repeated administration of lidocaine is no greater in pregnant than in nonpregnant patients.