EPIDURAL METABOLISM OF ARTICAINE TO ITS METABOLITE ARTICAINIC ACID IN5 PATIENTS AFTER EPIDURAL ADMINISTRATION OF 600 MG ARTICAINE

The clinical pharmacokinetics, metabolism and renal excretion of artic aine and its metabolite articainic acid have been investigated in man after epidural administration. (+/-)-Articaine and its metabolite (+/- )-articainic acid have different pharmacokinetic constants (P=0.0079) except for lag-time (t(lag); 0.06 min), first phase distribution of el imination (t1/2 alpha; 0.49 +/- 0.21 h), and elimination half life (t1 /2 beta; 2.19 +/- 0.98 h), which are all the same for both compounds. The total body clearance of articaine (103 +/- 57 L h(-1)) is 10 times higher than that of the metabolite articainic acid (10.7 +/- 1.80 L h (-1), P=0.0079). With similar half-life (t1/2 beta) values (2 h), the volumes of distribution (V-beta) are 10 times higher for the parent dr ug than for the metabolite ((329 +/- 212 L compared with 38.4 +/- 7.5 L, respectively; P=0.0079). The difference between the areas under the curves for total plasma articainic acid and that formed in the plasma gives an indication of the percentage metabolism during epidural tran sfer (5.38 +/- 1.51%). This percentage of metabolism corresponds to a mean epidural transfer time of 5 min. The main compound in the urine i s articainic acid (64.2 +/- 14.4%), followed by articainic acid glucur onide (13.4 +/- 4.97%) and the parent drug (1.45 +/- 0.77%). In total, 79.0 +/- 18.5% of the dose is recovered in the urine. The renal clear ance of articaine is 22.5 +/- 13.9 mL min(-1), whereas that of articai nic acid is 119.6 +/- 30.1 mL min(-1) (P<0.0001). The apparent renal c learance of articainic acid glucuronide was 25.4 +/- 12.0 mL min(-1). This value does not differ from that of the parent drug (P > 0.8). Art icainic acid glucuronide is not present in plasma, but has an apparent renal clearance of 25 mL min(-1). These results suggest that articain ic acid is glucuronidated by the tubular cells and then excreted.