Ropivacaine and its H-2(3)-labelled analogue - bioanalysis and disposition in healthy volunteers

The aim was to study the pharmacokinetic equivalence of the local anaesthetic ropivacaine and its stable isotope analogue [H-2(3)]-ropivacaine. Ropivacaine (40.0-53.0 mg) and [H-2(3)]-ropivacaine (41.9-52.4 mg) were given simultaneously to eight healthy subjects as a single i.v. infusion. Blood and urine samples were collected and the concentrations of ropivacaine and [H-2(3)]-ropivacaine were determined by gas chromatography-mass spectrometry (GC-MS) combined with an isotope dilution technique. The between-days accuracy was about 100% for both compounds and the between-days precisions were 3-13% and 5-11% for ropivacaine and [H-2(3)]-ropivacaine, respectively. The plasma concentrations at the end of the infusion were similar for both forms (about 1 mg l(-1)), as were clearance (about 475 mi min(-1)), volume of distribution at steady state (about 54 1) and terminal half-life (about 1.8 h). The 95% confidence intervals for the ratios (ropivacaine/[H-2(3)]-ropivacaine) of the individual parameters were in the range 0.90-1.10. It was concluded that ropivacaine and [H-2(3)]-ropivacaine are pharmacokinetically equivalent.