ROPIVACAINE AND ITS H-2(3)-LABELED ANALOG - BIOANALYSIS AND DISPOSITION IN HEALTHY-VOLUNTEERS

The aim was to study the pharmacokinetic equivalence of the local anae sthetic ropivacaine and its stable isotope analogue [H-2(3)]-ropivacai ne. 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 concentration s of ropivacaine and [H-2(3)]-ropivacaine were determined by gas chrom atography-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 t he 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 s teady 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 con cluded that ropivacaine and [H-2(3)]-ropivacaine are pharmacokinetical ly equivalent.