Note

High-performance liquid chromatography and preliminary pharmacokinetics of articaine and its 2-carboxy metabolite in human serum and urine

The interactions of the racemic mixture of articaine as well as pure (R)-articaine and pure (S)-articaine with monolayers of glycerophospholipids and brain lipids have been studied using the Langmuir monolayer technique. Articaine was added to the glycerophospholipids dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), 1-palmitoyl-2-oleoylphosphatidylserine (POPS) and total lipid extract from pig brain (TLPB). The amount of articaine in the monolayers was 30 mol%. The intercalation of each of the two enantiomers of articaine into a glycerophospholipid/brain lipid monolayers composed of chiral phospholipids will be diastereoisomeric in nature, hence different intercalation pattern for the two enantiomers can be expected. All the articaine species are found to intercalate into the DPPC monolayer and to increase the monolayer stability, this is most pronounced for the (R)-enantiomer. Intercalation of the articaine species into the DPPS monolayer increases the MMA and hardly affects the stability of the DPPS monolayer. In this monolayer, the articaine species intercalates into the head group region of the small and negatively charged serine head group, this is pronounced for the (R)-enantiomer. Our results indicate that by introducing an unsaturated acyl chain in the monolayer as in POPS, the monolayer discriminates between the articaine species. The (R)-enantiomer is located deep in the acyl chain region, whereas the (S)-enantiomer is found at or close to the head group. The data also might indicate that the (R)-enantiomer in the racemic mixture forms dimers in the POPS monolayer. Both articaine species as well as the racemic mixture intercalate into the monolayer of TLPB. Intercalation into this monolayer did not show any distinct difference in intercalation mode of the articaine species, probably due to camouflaging effect of large head groups like gangliosides and/or formation of lipid rafts in the monolayer. However, the (R)-enantiomer appears to intercalate better into the TLPB monolayer than the (S)-enantiomer. With proper standardization the Langmuir monolayer technique is a powerful method to discriminate between (R)- and (S)-enantiomer articaine interaction with model membranes.

The authors evaluated published evidence from controlled clinical trials regarding the efficacy of two local anesthetic solutions in providing successful pulpal anesthesia.

The authors searched MEDLINE and Embase databases to identify peer-reviewed randomized controlled trials in which researchers directly compared articaine and lidocaine local anesthetic solutions in adult participants. They extracted study characteristics and outcomes data as a basis for meta-analysis. They completed subgroup analyses for both infiltration and mandibular inferior alveolar block anesthetic techniques.

Articaine solutions had a probability of achieving anesthetic success superior to that of lidocaine, with an odds ratio of 2.44 (95 percent confidence interval [CI], 1.59–3.76; P < .0001). The greater odds ratio for articaine increased to 3.81 (95 percent CI, 2.71–5.36; P < .00001) when the authors analyzed only infiltration data. There was weaker, but still significant, evidence of articaine’s being superior to lidocaine for mandibular block anesthesia, with an odds ratio of 1.57 (95 percent CI, 1.12–2.21; P = .009), and no difference when the authors considered only symptomatic teeth.

Research evidence supports using articaine versus lidocaine for achieving pulpal anesthesia when the infiltration mode of administration is used. It is premature to recommend articaine for mandibular block anesthesia in cases involving irreversible pulpitis.

Articaine hydrochloride, 4-methyl-3-(2-[propylamino]propionamido)-2-thiophenecarboxylic acid, methyl ester hydrochloride, is a local anaesthetic commonly used in dentistry, and is classified as an amide local anaesthetic. Solid-state ¹³C and ³¹P NMR were used to investigate the uncharged articaine species (sample pH 10.0) when interacting with distearoylphosphatidylcholine (DSPC) model membranes. The DSPC phospholipid bilayer was studied at four different molar ratios of articaine, 10, 25, 40, and 55 mol%, respectively. The articaine concentration-dependent decrease in the DSPC bilayer gel-to-liquid-crystalline phase-transition temperature demonstrates substantial articaine interaction with this bilayer.

A DSPC bilayer contains a large hydrophobic core and the ¹³C and ³¹P NMR spectra of the 40 mol% articaine-containing sample demonstrate a disturbance in the molecular packing of the polar bilayer region that extends into the hydrophobic region, evidenced by carbon 2 and 3 of the stearoyl acyl chains. Observed ³¹P and ¹³C NMR spectral changes when articaine is increased from 40 to 55 mol%, suggest formation of articaine aggregates and decrease in DSPC bilayer perturbation at the latter articaine level.

Quicker onset and shorter elimination time favours (±) articaine as a short-acting local anaesthetic for regional anaesthesia in day-case settings, e.g. arthroscopy (shoulder, knee), hand and foot surgery, and dentistry, because patients treated with articaine will be ‘drug free’ more quickly than those who receive other local anaesthetics. Articaine diffuses better through soft tissue and bone than other local anaesthetics. The concentration of articaine in the alveolus of a tooth in the upper jaw after extraction was about 100 times higher than that in systemic circulation. Articaine is metabolised via hydrolysis into articainic acid, 75% of which in turn is excreted as such and 25% in the glucuronidated form by the kidneys.The half-lives of elimination (t_½α and t_½β) of articaine are 0.6 and 2.5 hours, whereas the apparent half-life of the metabolite articainic acid is 2.5 hours. Intrinsic half-lives of articainic acid are: t_½α 12 minutes, and t_½β 64 minutes (1 hour). In dentistry, articaine is the drug of choice in the vast majority of literature. In other regional anaesthesia techniques (intravenous regional anaesthesia, epidural, spinal and plexus blocks) there are not enough data to prove that (±) articaine is safer and more effective than the short-acting local anaesthetics lidocaine, (±) prilocaine or (±) mepivacaine.

Articaine is an amide local anesthetic introduced clinically in Germany in 1976 and subsequently throughout Europe, Canada and, in 2000, the United States.

The authors report on three identical single-dose, randomized, double-blind, parallel-group, active-controlled multicenter studies that were conducted to compare the safety and efficacy of articaine (4 percent with epinephrine 1:100,000) with that of lidocaine (2 percent with epinephrine 1:100,000).

A total of 1,325 subjects participated in these studies, 882 of whom received articaine 4 percent with epinephrine 1:100,000 and 443 of whom received lidocaine 2 percent with epinephrine 1:100,000. The overall incidence of adverse events in the combined studies was 22 percent for the articaine group and 20 percent for the lidocaine group. The most frequently reported adverse events in the articaine group, excluding postprocedural dental pain, were headache (4 percent), facial edema, infection, gingivitis and paresthesia (1 percent each). The incidence of these events was similar to that reported for subjects who received lidocaine. The adverse events most frequently reported as related to articaine use were paresthesia (0.9 percent), hypesthesia (0.7 percent), headache (0.55 percent), infection (0.45 percent), and rash and pain (0.3 percent each).

Articaine is a well-tolerated, safe and effective local anesthetic for use in clinical dentistry.

The authors compared the safety and efficacy of 4 percent articaine with epinephrine 1:100,000 with 2 percent lidocaine with epinephrine 1:100,000.

In three identical randomized, double-blind, multicenter trials, subjects 4 to 80 years of age received either 4 percent articaine with epinephrine 1:100,000 or 2 percent lidocaine with epinephrine 1:100,000 for simple or complex dental procedures. In each trial, the authors randomized the subjects in a 2:1 ratio to receive articaine or lidocaine. Efficacy was determined by both subject and investigator using a visual analog scale, or VAS. The authors used the Kruskal-Wallis test to analyze the data.

A total of 882 subjects received articaine, and 443 received lidocaine. The authors found no statistical differences between the groups (P = .05). They also compared drug volumes for both articaine and lidocaine groups (2.5 milliliters ± 0.07 standard error of mean, or SEM, vs. 2.6 mL ± 0.09 SEM for simple procedures and 4.2 mL ± 0.15 SEM vs. 4.5 mL ± 0.21 SEM for complex procedures). The procedures&apos; durations were comparable for both the articaine and lidocaine groups. The authors found no statistical difference between the two treatment groups (P = .05) with respect to subject or investigator pain ratings using the VAS; the mean pain scores determined by both patients and investigators for all groups tested were less than 1.0.

The authors found that 4 percent articaine with epinephrine 1:100,000 was well-tolerated in 882 subjects. It also provided clinically effective pain relief during most dental procedures and had a time to onset and duration of anesthesia appropriate for clinical use and comparable to those observed for other commercially available local anesthetics.

Pain control is a major component of patient comfort and safety. Local anesthetics form the backbone of pain control techniques in dentistry. Four percent articaine with epinephrine is an amide local anesthetic that will meet the clinical requirements for pain control of most dental procedures in most patients.