Summary

Background and objective: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration.

Methods: Eight volunteers (18–32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23–85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration–time data were analysed by compartmental and non-compartmental analysis.

Results: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00–1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00–1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean ± SD: 196 ± 65 min), total body clearance (349 ± 114 mL min−1) and volume of distribution at steady state (56 ± 14 L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fraction absorbed and half-life of the fast absorption process were 0.22 ± 0.06 and 5.2 ± 2.7 min, respectively. The values for the slow absorption process were 0.84 ± 0.14 and 386 ± 91 min, respectively.

Conclusions: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Summary

Background and objective: To evaluate the efficacy, delay and duration of analgesia of three equianalgesic epidural doses of levobupivacaine, ropivacaine and bupivacaine during the first stage of labour.

Methods: One hundred and twenty-nine healthy primigravida in spontaneous labour who requested epidural analgesia were enrolled in a randomized observer-blinded study. Parturients were allocated to receive epidural levobupivacaine 0.0625%, ropivacaine 0.1% or bupivacaine 0.0625%. Sufentanil 10 μg was added to all solutions; the total volume of epidural solution was 20 mL. Pain was measured using a 100 mm visual analogue pain scale immediately before the epidural block, and at 5, 10, 15, 20 and 30 min thereafter. Motor block was evaluated using a modified Bromage scoring system. The adequacy of motor function for ambulation was also evaluated. Delay of analgesia was the time interval between the injection of the solution and the first painless contraction. Duration of analgesia was the time from the first painless contraction to the parturients' requests for further analgesia.

Results: Twelve parturients failed to complete the study. Eleven parturients had inadequate analgesia (four in Group Levobupivacaine, four in Group Ropivacaine and three in Group Bupivacaine; P > 0.05). Data was analysed from 34 parturients in Group Levobupivacaine, from 37 in Group Ropivacaine and from 35 in Group Bupivacaine. There were no differences in the delay of analgesia or in the number of parturients who were able to walk unaided. Levobupivacaine and ropivacaine produced more prolonged analgesia than bupivacaine (114 and 119 min, respectively, versus 89 min; P < 0.01).

Conclusions: During early labour, equipotent low concentrations of levobupivacaine, ropivacaine and bupivacaine, all with the addition of sufentanil 10 μg, produced similar pain relief and motor block, but levobupivacaine and ropivacaine produced a longer lasting analgesia. About 10% of parturients had inadequate analgesia with a single bolus of the tested solutions.