title: Epidural metabolism of articaine to its metabolite articainic acid in five patients after epidural administration of 600 mg articaine.
abstract: The clinical pharmacokinetics, metabolism and renal excretion of articaine 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 (tlag; 0.06 min), first phase distribution of elimination (t 1/2 alpha; 0.49 +/- 0.21 h), and elimination half life (t 1/2 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 (t 1/2 beta) values (2h), the volumes of distribution (V beta) are 10 times higher for the parent drug 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 transfer (5.38 +/- 1.51%). This percentage of metabolism corresponds to a mean epidural transfer time of 5 min. The main compound in the urine is articainic acid (64.2 +/- 14.4%), followed by articainic acid glucuronide (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 clearance of articaine is 22.5 +/- 13.9 mL min-1, whereas that of articainic acid is 119.6 +/- 30.1 mL min-1 (P < 0.0001). The apparent renal clearance 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). Articainic acid glucuronide is not present in plasma, but has an apparent renal clearance of 25 mL min-1. These results suggest that articainic acid is glucuronidated by the tubular cells and then excreted.
authors.affiliation: Institute for Anaesthesiology, Academic Hospital Nijmegen Sint Radboud, Nijmegen, The Netherlands.
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: G E
authors.initials: GE
authors.lastname: Van Oss
authors.forename: M J
authors.initials: MJ
authors.lastname: Gielen
authors.forename: L H
authors.initials: LH
authors.lastname: Booij
mesh_terms: D000328:Adult; D000368:Aged; D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002355:Carticaine / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
chemical_list: D000779:Anesthetics, Local; D002355:Carticaine