Epidural Metabolism of Articaine to its Metabolite Articainic Acid in Five Patients after Epidural Administration of 600 mg Articaine

• Published in: Journal of pharmacy and pharmacology 1997-02, Vol.49 (2), p.158-163
• Main Authors: VREE, TOM B., VAN OSS, GERTJAN E. C. J. M., GIELEN, MATHIEU J. M., BOOIJ, LEO H. D. J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anesthesia, Epidural; Anesthetics, Local - pharmacokinetics; Anesthetics. Neuromuscular blocking agents; Area Under Curve; Biological and medical sciences; Biological Availability; Carticaine - pharmacokinetics; Female; Half-Life; Humans; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.1997.tb06772.x

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 = 00079) except for lag‐time (tlag; 0.06 min), first phase distribution of elimination (t½α; 0.49 ± 0.21 h), and elimination half life (t½α; 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 (t½β) values (2 h), the volumes of distribution (Vβ) 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.