Pharmacokinetics and transplacental transfer of lidocaine and its metabolite for perineal analgesic assistance to pregnant women

Abstract

Background: Obstetrical analgesia continues to be challenging to science in the search for safe and effective methods that will permit the use of these procedures allied to improved obstetrical and perinatal results.

Objective: The objective of the present study was to investigate the pharmacokinetics and the placental transfer of lidocaine and its metabolite in parturients whose pregnancies were resolved by the vaginal route under perineal analgesia.

Patients and methods: The study was conducted on 23 pregnant women who received perineal analgesia with 20 ml 2% lidocaine (400 mg) during the expulsive period of labor. Maternal venous blood samples were obtained from 0 min to 360 min after drug administration, and umbilical venous blood was obtained at delivery. Lidocaine and monoethylglycinexylidide (MEGX) were determined using high-performance liquid chromatography. The fetal/maternal ratios of the drugs were determined on the basis of maternal and fetal concentrations at delivery.

Results: Maximum lidocaine concentrations at the median times of 15 min were 3.22 microg/ml. The pharmacokinetic parameters were: half-life t1/2alpha 24.0 min, area under the curve (AUC)0-infinity 460.2 microg/min per ml, t1/2beta 180.0 min, clearance 12.2 ml/min per kg and volume distribution 3.1 l/kg. The fetal/maternal ratio for lidocaine at delivery was 0.46, with the latency time between drug administration and delivery being 11.0 min. Maximum MEGX concentrations at the median time of 90 min were 229.0 ng/ml. The t1/2 for MEGX was 240 min, and AUC0-infinity was 82.4 microg min/ml.

Conclusion: Lidocaine administered by the perineal route presented a tmax of 15 min, significantly lower than when the drug was administered peridurally, revealing that the time between administration and the occurrence of the analgesic effect was shorter. The study demonstrated placental transfer of lidocaine at ratios of about 50% for lidocaine at the time of delivery. The MEGX placental transfer demonstrated fetal concentration higher than the maternal at the time of delivery.