psd-502 and 2-toluidine

Oraqix, a novel non-injectable anesthetic gel containing lidocaine and prilocaine and a thermosetting agent has been developed to provide localized anesthesia in periodontal pockets during scaling/root planing (SRP). The aim of this open study was to determine the plasma levels of lidocaine and prilocaine following application of 8.5 g Oraqix (5 cartridges) to 11 patients with generalized periodontitis (> or = 49% of tooth pockets > or = 5 mm and > or = 23% of pockets > or = 6 mm). Oraqix was applied to the pockets during periodontal probing and SRP over a 2.6 3.4 h period. Blood samples were collected up to 10 h after the start of application of Oraqix. Peak plasma levels of lidocaine (0.16-0.55 mg/L) and prilocaine (0.05-0.18 mg/L) occurred 2.0-3.7 h and 2.0-3.3 h, respectively, after the start of application of Oraqix. These levels are well below threshold levels for initial signs of central nervous system (CNS) toxicity. In conclusion, application of 8.5 g Oraqix (212.5 mg of lidocaine base and 212.5 mg of prilocaine base) in periodontal pockets was well tolerated and displayed a wide safety margin with respect to plasma levels normally associated with systemic toxicity.

Topics: Adult; Aged; Anesthesia, Dental; Anesthetics, Combined; Anesthetics, Local; Dental Scaling; Female; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobin; Middle Aged; Periodontal Pocket; Prilocaine; Toluidines

Oraqix, a new non-injection local anesthetic, lidocaine/prilocaine gel 5%, has been developed to provide pain relief in association with periodontal probing and scaling/root planing (SRP). The aim of this open study was to describe the plasma profiles of lidocaine and prilocaine following a single dose of Oraqix to patients with advanced periodontitis.. 10 patients with 18 to 28 teeth with pocket depths of at least 4 mm were included. Oraqix was applied in the pockets around all the teeth in the mouth by means of a blunt applicator. The total dose applied per patient was 0.9 to 3.5 g. Directly thereafter all the pockets were probed and 3 teeth subjected to SRP. The mouth was rinsed out with a glass of water 20-27 min after the application of the gel. Blood samples were collected before and up to 90 min after the start of application of Oraqix.. Peak plasma concentrations of lidocaine (99-266 ng/ml) and prilocaine (46-118 ng/ml) occurred 20-40 min after the start of application. These levels were low compared to those reported to cause initial signs of CNS toxicity (5000-6000 ng/ml). Side-effects were few and mild local effects of short duration.. In conclusion, there is a large safety margin with respect to systemic effects following the application of up to 3.5 g Oraqix in periodontal pockets.

Topics: Administration, Topical; Adult; Anesthetics, Combined; Anesthetics, Local; Aniline Compounds; Chromatography, Liquid; Dental Scaling; Female; Follow-Up Studies; Gels; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Linear Models; Male; Mass Spectrometry; Middle Aged; Mouthwashes; Periodontal Pocket; Periodontitis; Prilocaine; Regression Analysis; Root Planing; Safety; Toluidines; Water

EMLA (eutectic mixture of lidocaine and prilocaine) cream is currently not recommended for use in infants < 1 month of age because of the potential risk of methemoglobinemia as a result of the o-toluidine metabolite of prilocaine. We studied bioavailability and changes in methemoglobin levels following topical penile exposure to 1 g of EMLA cream for 1 hour in piglets. Lidocaine, prilocaine, and o-toluidine concentrations were measured simultaneously using a high-performance liquid chromatography method. The systemic bioavailability of EMLA was low: 4.0 +/- (SD) 4.7% for lidocaine (range 0-13.6; n = 8) and 7.2 +/- 5.7% for prilocaine (range 0-14.5; n = 8). The ratio between exposure to o-toluidine with EMLA versus intravenous administration (i.e., AUCEMLA/AUCIV; see text) was also low: 4.2 +/- 9.3% (range 0-28.6; n = 9). The mean maximum methemoglobin value after intravenous administration was 1.23 +/- 0.64% (range 0.5-3.0; n = 12) and after penile application 0.99 +/- 0.36% (range 0.5-2.0; n = 12). The methemoglobin value was elevated significantly above baseline after intravenous administration (p = 0.03), but not after penile application of EMLA. These findings suggest that penile administration of 1 g of EMLA may be safe for neonatal circumcision, but further study is required.

Topics: Absorption; Anesthetics, Local; Animals; Animals, Newborn; Circumcision, Male; Cross-Over Studies; Drug Combinations; Injections, Intravenous; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Methemoglobinemia; Ointments; Penis; Prilocaine; Swine; Toluidines