Does Gestational Age Affect the Pharmacokinetics and Pharmacodynamics of Lidocaine in Mother and Fetus?

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Abstract
The pharmacokinetics and pharmacodynamics of lidocaine were studied in nine chronically prepared pregnant ewes and their fetuses at a mean (.+-.SE) gestation of 119 .+-. 1.0 days, and the results were compared to the data previously published from ten animals at 138 .+-. 1.2 days of gestation (term 148 days). Lidocaine was infused intravenously to the mother at a constant rate of 0.1 mg .cntdot. kg-1 .cntdot. min-1 over a period of 180 in, in order to reach a steady-state maternal plasma lidocaine concentration of approximately 2 .mu.g/ml. Maternal and fetal blood samples and maternal urine were collected at intervals throughout the infusion for determination of pH, blood gases, and lidocaine concentrations. Maternal and fetal heart rate, blood pressure, and intraamniotic pressure were continuously recorded. Fetal cardiac output and organ blood flow were determined before and at the end of lidocaine infusion using radionuclide-labeled microspheres. Lidocaine tissue concentrations were determined in several maternal and fetal organs excised at the end of infusion. In both groups, the steady-state plasma concentrations of lidococaine were similar; namely, 2.3 .+-. 0.17 and 2.1 .+-. 0.21 .mu.g/ml in preterm and term ewes, respectively. There were also no significant differences in steady-state plasma drug concentrations in preterm and term fetuses (1.3 .+-. 0.11 and 1.2 .+-. 0.15 .mu.g/ml). The mean fetal maternal concentration ratios (F/M) were the same; namely, 0.6. Maternal urinary excretion of lidocaine correlated with urine pH, being greater in the more acid urine. Tissue uptake of drug tended to be higher in the preterm than term mothers, but only significantly so in the brain and adrenals. In the fetuses, tissue uptake was similar in both groups except in the lungs and liver, where it was higher at term. Liver uptake was significantly higher in the fetuses than in the corresponding ewes. Maternal and fetal vital signs and blood gases, as well as the fetal cardiac output and organ blood flow, were not altered by lidocaine infusion. It is concluded that the pharmacokinetics and dynamics of lidocaine in the mother and fetus are not affected by maturation between 80% and 95% of gestation.

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