Lidocaine hydrochloride (10 nM; 48 hours) greatly decreases cell proliferation [2]. Lidocaine hydrochloride (1-10 nM; 24-72 hours) decreases cell viability, attaining the highest inhibitory impact at a concentration of 10 nM and 48 treatment times [2] Lidocaine hydrochloride (10 nM; 48 hours) dramatically increases cell viability. Sterilization rate[2]. Lidocaine hydrochloride (10 nM; 48 hours) suppresses cyclin D1 and dramatically upregulates p21 expression [2].

In the stent, lidocaine hydrochloride causes a total reverse tail nerve block. The mechanical pain blockade caused by lidocaine hydrochloride had a shorter onset and quicker recovery than thermal pain blockade [3].

Cell proliferation analysis[2].
Cell Types: human gastric cancer cell line MKN45
Tested Concentrations: 10 nM
Incubation Duration: 48 hrs (hours)
Experimental Results: Cell proliferation diminished Dramatically.

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Cell viability assay [2]
Cell Types: human gastric cancer cell line MKN45
Tested Concentrations: 1, 5 and 10 nM
Incubation Duration: 24, 48, 72 hrs (hours)
Experimental Results: Inhibition of MKN45 cell viability.

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Cell apoptosis analysis [2]
Cell Types: Human gastric cancer cell line MKN45
Tested Concentrations: 10 nM
Incubation Duration: 48 hrs (hours)
Experimental Results: The cell apoptosis rate increased Dramatically.

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Western Blot Analysis [2]
Cell Types: human gastric cancer cell line MKN45
Tested Concentrations: 10 nM
Incubation Duration: 48 hrs (hours)
Experimental Results: Cyclin D1 expression was Dramatically down-regulated, and p21 expression was Dramatically up-regulated.

Absorption, Distribution and Excretion
Generally, lidocaine is readily absorbed through mucous membranes and damaged skin, but poorly absorbed through intact skin. The drug is rapidly absorbed into the bloodstream from the upper respiratory tract, tracheobronchial tree, and alveoli. Although lidocaine is also well absorbed from the gastrointestinal tract, its oral bioavailability is only about 35% due to its high first-pass metabolism. After injection into tissues, lidocaine is also rapidly absorbed, with the absorption rate influenced by vascular distribution and specific tissues and fats that can bind lidocaine. Blood lidocaine concentrations are subsequently affected by various factors, including the rate of absorption from the injection site, the rate of tissue distribution, and the rates of metabolism and excretion. Systemic absorption of lidocaine then depends on the injection site, the administered dose, and its pharmacological properties. Peak blood concentrations occur after intercostal nerve block, followed by lumbar epidural space, brachial plexus, and subcutaneous tissue. Regardless of the injection site, the total injected dose is the primary determinant of absorption rate and blood concentration. The injected dose of lidocaine shows a linear relationship with the final peak plasma concentration. However, studies have found that lidocaine hydrochloride is completely absorbed after parenteral administration, and its absorption rate depends on lipid solubility and the presence of vasoconstrictors. Besides intravenous administration, the highest plasma concentration is observed after intercostal nerve block, and the lowest plasma concentration is observed after subcutaneous administration. Furthermore, lidocaine can cross the blood-brain barrier and placental barrier, presumably via passive diffusion. Untreated lidocaine and its metabolites are primarily excreted by the kidneys, with less than 5% of the drug remaining in the urine. Renal clearance is negatively correlated with protein binding affinity and urine pH. The latter suggests that lidocaine excretion occurs via non-ionic diffusion. The volume of distribution of lidocaine is 0.7 to 1.5 L/kg. Specifically, lidocaine is distributed in systemic water. Its clearance rate from the blood can be described using a two-compartment model or even a three-compartment model. There is a rapid clearance phase (α phase), which is thought to be associated with uptake in rapidly at-equilibrium tissues (e.g., tissues with high vascular perfusion). A slower distribution phase is associated with distribution to tissues with slow at-equilibrium (β phase) and their metabolism and excretion (γ phase). Lidocaine is ultimately distributed throughout the body. Generally, higher concentrations are found in organs with higher perfusion. Skeletal muscle has the highest concentrations, primarily due to muscle mass rather than drug affinity. A study of 15 adults showed that the mean systemic clearance of intravenously administered lidocaine was approximately 0.64 ± 0.18 L/min. The binding rate of lidocaine to plasma proteins varies among individuals and is concentration-dependent. At concentrations of 1–4 μg/mL, the binding rate to plasma proteins is approximately 60–80%. Lidocaine partially binds to α1-acid glycoprotein (α1-AGP), and the degree of binding depends on the plasma concentration of this protein. In patients with myocardial infarction, elevated plasma α1-acid glycoprotein (α1-AGP) concentrations were associated with increased lidocaine binding and elevated total plasma drug concentrations, but only a slight increase in free drug plasma concentrations. These changes in α1-AGP concentrations and lidocaine binding are thought to partially explain the drug accumulation observed in myocardial infarction patients receiving prolonged infusions. In patients with congestive heart failure, the volume of distribution of lidocaine decreased; while in patients with liver disease, the volume of distribution increased. Lidocaine is widely distributed throughout the body. Following intravenous bolus injection, plasma drug concentrations rapidly decline, primarily due to distribution to highly perfused tissues such as the kidneys, lungs, liver, and heart; a slower elimination phase then occurs, during which the drug is metabolized and redistributed to skeletal muscle and adipose tissue. Lidocaine has a high affinity for fat and adipose tissue. As plasma drug concentrations decrease, the tissue-to-blood diffusion gradient increases, and lidocaine initially entering highly perfused tissues and adipose tissue diffuses back into the bloodstream. The plasma lidocaine concentration required to suppress ventricular arrhythmias is approximately 1-5 μg/mL. Toxic reactions may occur at plasma lidocaine concentrations above 5 μg/mL. Following intravenous injection of 50-100 mg lidocaine hydrochloride, the drug takes effect within 45-90 seconds, with a duration of action of 10-20 minutes. If intravenous infusion is initiated without an initial bolus dose, the time required to reach therapeutic plasma concentrations is relatively long. For example, without a loading dose, a continuous infusion at a rate of 60-70 μg/kg/min may take 30-60 minutes to reach therapeutic plasma concentrations. It has been reported that in cardiac patients, an initial intravenous bolus of 1.5 mg/kg, followed by a continuous infusion at a rate of 50 μg/kg/min, can maintain plasma concentrations between 1.5-5.5 μg/mL. For more complete data on the absorption, distribution, and excretion of lidocaine (17 types), please visit the HSDB records page.

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Metabolic/Metabolic Substances
Lidocaine is primarily metabolized rapidly in the liver, with both metabolites and the parent drug excreted via the kidneys. Biotransformation includes oxidative N-dealkylation, cyclohydroxylation, amide bond cleavage, and conjugation reactions. N-dealkylation is the main biotransformation pathway, yielding the metabolites monoethylglycyldimethylamine and glycyldimethylamine. The pharmacological/toxicological effects of these metabolites are similar to those of lidocaine hydrochloride, but less potent. Approximately 90% of lidocaine hydrochloride is excreted as various metabolites after administration, with less than 10% excreted unchanged. The main metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.
Approximately 90% of parenteral doses of lidocaine are rapidly metabolized in the liver, first via deethylation to generate MEGX and GX, followed by amide bond cleavage to generate dimethylamine and 4-hydroxydimethylamine, ultimately excreted in the urine. Less than 10% of the dose is excreted unchanged in the urine.
Lidocaine metabolism rates may also be reduced in patients with liver disease, possibly due to altered liver perfusion or liver tissue necrosis. The distribution and clearance of lidocaine and its metabolite monoethylglycyldimethylamine (MEGX) appear to remain normal in patients with renal failure, but glycyldimethylamine (GX) may accumulate in these patients after several consecutive days of intravenous lidocaine administration.
…This study aimed to determine the levels of lidocaine and its metabolite monoethylglycyldimethylamine (MEGX) in breast milk following local anesthesia for dental surgery. The study included seven lactating mothers (aged 23–39 years) who received 3.6–7.2 mL of 2% lidocaine (without epinephrine). High-performance liquid chromatography (HPLC) was used to determine the concentrations of lidocaine and its metabolite MEGX in blood and breast milk. The milk-to-plasma concentration ratio and the daily dose of lidocaine and MEGX that the infant might ingest were calculated. Two hours after injection, the lidocaine concentration in maternal plasma was 347.6 ± 221.8 ug/L; three hours after injection, the lidocaine concentration in breast milk was 120.5 ± 54.1 ug/L; six hours after injection, the MEGX concentration in maternal milk was 58.9 ± 30.3 ug/L; three hours after injection, the MEGX concentration in breast milk was 97.5 ± 39.6 ug/L; and six hours after injection, the MEGX concentration in maternal milk was 52.7 ± 23.8 ug/L. Based on these data, and considering an intake of 90 ml of breast milk every 3 hours, the daily lidocaine and MEGX doses ingested by the infant were 73.41 ± 38.94 μg/L/day and 66.1 ± 28.5 μg/L/day, respectively. This study demonstrates that even if a lactating mother receives dental treatment with lidocaine local anesthesia without adrenaline, she can safely continue breastfeeding. To determine the time/concentration profiles of lidocaine and its active metabolites glycine-xyleneamine (GX) and monoethylglycine-xyleneamine (MEGX) during a 96-hour lidocaine infusion, we administered lidocaine to eight healthy adult horses via continuous infusion (0.05 mg/kg body weight/min) for 96 hours. Serum concentrations of lidocaine, GX, and MEGX were determined by high-performance liquid chromatography (HPLC) during and after infusion. Serum lidocaine concentrations reached steady state at 3 hours, with no accumulation observed thereafter. Concentrations were above the target therapeutic concentration (980 ng/mL) only at 6 and 48 hours, and did not reach potentially toxic levels (>1850 ng/mL) at any time point. MEGX did not accumulate over time, while GX accumulated significantly within 48 hours, then remained stable. Within 24 hours of discontinuation, serum concentrations of lidocaine, MEGX, and GX were all below the detection limit. No horses exhibited signs of lidocaine poisoning during the study period. Prolonged infusion did not significantly affect lidocaine metabolism, and no adverse reactions were observed. Prolonged infusion appears to be safe for normal horses, but the accumulation of the potentially toxic metabolite GX is a concern.
For more complete data on the metabolism/metabolites of lidocaine (11 in total), please visit the HSDB records page.
Known human metabolites of lidocaine include monoethylglycyldimethylamine and 3-hydroxylidocaine.
Primarily metabolized in the liver.
Excretion route: Lidocaine and its metabolites are excreted via the kidneys.
Half-life: 109 minutes

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Biological half-life
The elimination half-life of lidocaine hydrochloride after intravenous bolus injection is typically 1.5 to 2.0 hours. Because lidocaine hydrochloride is rapidly metabolized, any disease affecting liver function can alter its pharmacokinetics. The half-life may be twice or more prolonged in patients with hepatic impairment.
...In 30 patients who underwent surgery (aged 18–70 years)...the mean half-life of lidocaine was...94 minutes.
...It has been reported that the half-lives of both lidocaine and MEGX are prolonged in patients with myocardial infarction (with or without heart failure); it has also been reported that the half-life of GX is prolonged in patients with heart failure secondary to myocardial infarction. The half-life of lidocaine has also been reported to be prolonged in patients with congestive heart failure or liver disease, and may also be prolonged after continuous intravenous infusion exceeding 24 hours. The initial half-life of lidocaine is 7–30 minutes, and the terminal half-life is 1.5–2 hours. In healthy individuals, the elimination half-lives of its active metabolites, monoethylglycyl dimethylamine (MEGX) and glycyl dimethylamine (GX), are 2 hours and 10 hours, respectively… Lidocaine is primarily metabolized in the liver; liver disease and reduced hepatic blood flow prolong its half-life. In dogs, its half-life is typically less than 1 hour. The average elimination half-life of lidocaine in newborns after maternal epidural anesthesia is 3 hours.

Toxicity Summary
Identification and Uses: Lidocaine is a white or slightly yellow crystalline powder or needle-like substance with a characteristic odor. It is commonly used as a medicine, including as a local anesthetic, antiarrhythmic, or voltage-gated sodium channel blocker. Lidocaine can also be used to treat hypertensive emergencies or acute coronary syndromes associated with the toxicity of various stimulants and antiarrhythmics. Lidocaine transdermal patches are used to relieve postherpetic neuralgia. Oral patches can be applied to the oral mucosa before superficial dental procedures. A mixture of lidocaine (2.5%) and prilocaine (2.5%) is used in occlusive dressings as an anesthetic before intravenous punctures, skin grafts, and genital infiltration anesthesia. A combination of lidocaine and tetracaine produces an "exfoliating" effect and is approved for local analgesia before superficial dermatological procedures. Human Exposure and Toxicity: Due to its rapid entry into the brain, adverse effects primarily affect the central nervous system. Central nervous system adverse reactions may manifest as drowsiness, dizziness, disorientation, confusion, lightheadedness, tremors, psychosis, tension, anxiety, agitation, euphoria, tinnitus, visual disturbances (including blurred or double vision), nausea, vomiting, paresthesia (such as itching, coldness, or numbness), dysphagia, dyspnea, and slurred speech. In addition, muscle twitching or tremors, seizures, loss of consciousness, coma, respiratory depression, and respiratory arrest may also occur. Following lidocaine poisoning, cardiovascular effects may also occur shortly after the onset of central nervous system effects. If supportive care is provided during this period, the drug will rapidly spread from the heart, and cardiac function will spontaneously recover. Lidocaine may induce seizures in infants. Neonatal lidocaine poisoning, usually caused by accidental injection of the drug into the scalp or skull during local anesthesia (tail or paracervical block or episiotomy), can cause respiratory arrest, hypotonia, and seizures. Mydriasis and loss of oculomotor reflexes may also be observed. These effects are more severe when serum lidocaine concentrations exceed 5 μg/mL, and paresthesia or drowsiness usually precedes these effects. With continuous use of four 5% lidocaine patches, changed every 12 or 24 hours for 72 hours, most patients experienced only mild erythema at the patch site, with no systemic adverse reactions. No loss of sensation at the patch site was reported. In healthy volunteers, patients with postherpetic neuralgia, and patients with acute herpes zoster, systemic exposure to lidocaine and its major active metabolite, monoethylglycyl dimethylamine (MEGX), was extremely low after use of lidocaine gel or patch. In human SH-SY5Y neuroblastoma cells, local anesthesia led to rapid cell death, primarily due to necrosis. Lidocaine can induce apoptosis by prolonging exposure time or increasing concentration. Animal studies: In rats, epidural lidocaine injection resulted in less persistent functional impairment and histological damage to nerve roots and the spinal cord compared to intrathecal lidocaine injection. In eight New Zealand rabbits, injection of 0.2 mL of 1% lidocaine hydrochloride into the anterior chamber of the lens resulted in morphological abnormalities in both the cornea and iris of the injected eye. Another experiment involving injection of 2% lidocaine hydrochloride into the rabbit corneal endothelium showed that lidocaine caused statistically significant corneal thickening and clinically significant corneal opacity. Injection of lidocaine into the dorsal root ganglion of rats induced hyperalgesia, possibly due to activation of resident satellite glial cells. Exposure of primary rabbit urothelial cell (PRUC) cultures to 0.5% or 1.0% lidocaine for one hour decreased cell viability. Lidocaine rapidly crosses the placenta in pregnant guinea pigs. High concentrations of lidocaine were detected in the liver, heart, and brain of the fetus. Excessive drug concentrations in the fetal myocardium may be one reason for the significant inhibitory effect of local anesthetics. Another study showed that rats receiving continuous intravenous infusion of lidocaine two weeks before mating and throughout gestation did not show significant effects on their offspring. Furthermore, in pregnant ewes receiving continuous intravenous lidocaine infusion, pregnancy did not enhance the central nervous system and cardiovascular toxicity of lidocaine compared to non-pregnant ewes. In a somatic mutation and recombination assay of the wings of Drosophila melanogaster, lidocaine did not induce genotoxicity. This assay can detect point mutations, chromosomal mutations, and recombinations caused by direct and indirect genotoxin effects. 0.25% lidocaine reduced cell viability and caused DNA degradation in mouse 3T6 fibroblasts. Topical application of lidocaine to the dorsal skin of mice weekly for 26 weeks did not show carcinogenicity. Lidocaine exerts its local anesthetic effect by stabilizing the neuronal membrane by inhibiting the ion flow required for nerve impulse initiation and conduction. Lidocaine alters signal transduction in neurons by blocking fast-voltage-gated sodium (Na+) channels responsible for signal transduction on the neuronal cell membrane. When the blockade is sufficient, the postsynaptic neuronal membrane cannot depolarize, thus preventing the transmission of action potentials. The mechanism of action of this anesthetic is not merely to prevent pain signals from reaching the brain, but to block the generation of pain signals at their source.

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Toxicity Data
LD50: 459 (346-773) mg/kg (oral, non-fasting female rats)
LD50: 214 (159-324) mg/kg (oral, fasting female rats)

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Interactions
EMLA cream is a topical formulation based on a eutectic mixture of lidocaine and prilocaine, used clinically for local analgesia under occlusive dressings. Skin pallor has been reported after topical application, but it is unclear whether this reaction is caused by the anesthetic mixture, the excipients, or the occlusive dressing. This study employed a double-blind randomized controlled trial to observe the pallor-inducing effect of EMLA cream versus placebo after 1 hour under occlusive dressings in 50 healthy volunteers, with each participant serving as a self-control. The results showed that leukocytosis occurred in 33 cases (66%) in the EMLA cream group and only 3 cases (6%) in the placebo group, a highly statistically significant difference. Leukocytosis occurred immediately after dressing removal and was very transient, disappearing within 3 hours in all cases. It was concluded that leukocytosis (1) was prevalent but very transient; and (2) was caused by the anesthetic mixture contained in the EMLA cream, rather than solely by the excipients or the occlusive dressing, as this reaction was not observed in the placebo group. The exact mechanism of this reaction remains unclear. Recent studies have shown that cytochrome P-450 isoenzyme 1A2 plays an important role in the biotransformation of lidocaine. This study investigated the effect of the cytochrome P-450 1A2 inhibitor ciprofloxacin on the pharmacokinetics of lidocaine. In a randomized, double-blind, crossover study, nine healthy volunteers received 500 mg of ciprofloxacin or placebo orally twice daily for 2.5 consecutive days. On day 3, participants received a single intravenous infusion of 1.5 mg/kg lidocaine over 60 minutes. Plasma concentrations of lidocaine, 3-hydroxylidocaine, and monoethylglycylxylmethylamine were measured within 11 hours of the start of lidocaine infusion. Ciprofloxacin increased the mean peak concentration and area under the plasma concentration-time curve (AUC) of lidocaine by 12% (range -6% to 46%; P < 0.05) and 26% (8% to 59%; P > 0.01), respectively. Ciprofloxacin decreased the mean plasma clearance of lidocaine by 22% (7% to 38%; P < 0.01). Ciprofloxacin decreased the AUC of monoethylglycylxylmethylamine by 21% (P < 0.01) and the AUC of 3-hydroxylidocaine by 14% (P < 0.01). Concomitant administration of ciprofloxacin after intravenous lidocaine administration slightly delayed its plasma decay. Ciprofloxacin may increase the systemic toxicity of lidocaine. Epinephrine is often added to lidocaine solutions to prolong the duration of spinal anesthesia. Although this use is common, the neurotoxic effects of epinephrine on this anesthetic are unclear. This study aimed to investigate whether the addition of epinephrine after intraspinal injection of lidocaine exacerbated functional impairment or histological damage in rats. Eighty rats were randomly divided into four groups and administered intrathecal injections of 5% lidocaine, 5% lidocaine containing 0.2 mg/mL epinephrine, 0.2 mg/mL epinephrine, or saline alone. Tail-flick tests were performed 4 and 7 days post-injection to assess persistent sensory impairment. The animals were then sacrificed, and spinal cord and nerve roots were prepared for neuropathological evaluation. The results showed that rats injected with 5% lidocaine developed persistent sensory impairment and histological damage, and the addition of epinephrine significantly aggravated the damage. Sensory function in rats in the epinephrine group without anesthetic was similar to baseline and not significantly different from the saline group. Histological changes in rats injected with epinephrine alone were not significantly different from the saline control group. The neurotoxicity of intrathecal lidocaine is enhanced by the addition of epinephrine. The presence of epinephrine in the solution may need to be considered when developing clinical recommendations for the maximum safe intrathecal dose of this anesthetic.
Objective: During continuous epidural anesthesia with lidocaine, the concentration of plasma monoethylglycyldimethylamine (MEGX), the active metabolite of lidocaine, continues to rise. This study aimed to evaluate the effect of epinephrine on lidocaine absorption and MEGX accumulation during continuous epidural anesthesia in children. Anesthesia was administered via an initial bolus of 5 mg/kg of 1% lidocaine solution, followed by a continuous infusion at a rate of 2.5 mg/kg/hr. Patients in the control group (n = 8) received lidocaine alone, while patients in the epinephrine group (n = 8) received lidocaine combined with epinephrine (5 μg/mL). The concentrations of lidocaine and its active metabolite MEGX in plasma samples collected at 15 minutes, 30 minutes, and 1, 2, 3, 4, and 5 hours post-infusion were determined using high-performance liquid chromatography-ultraviolet (HPLC-UV) detection. Within 1 hour post-infusion, the lidocaine concentration in the control group was higher than that in the epinephrine group; however, after 2 hours, there was no significant difference in lidocaine concentration between the two groups. Plasma MEGX levels in both groups remained elevated, with the MEGX concentration in the control group being significantly higher than that in the epinephrine group. Within 2 hours post-infusion, the total concentrations of lidocaine and MEGX in the plasma of the control group were higher than those in the epinephrine group, but after 3 hours, there was no significant difference between the two groups. The potential for reducing systemic toxicity by adding epinephrine to lidocaine is limited, as the combined reduction in plasma concentrations of lidocaine and its active metabolite MEGX is small and limited to the initial phase of infusion. For more complete interaction data (out of 33) on lidocaine, please visit the HSDB record page. Non-human toxicity values: Mouse oral LD50: 292 mg/kg; Mouse intraperitoneal LD50: 105 mg/kg; Mouse intravenous LD50: 19.5 mg/kg; Rat oral LD50: 317 mg/kg. For more complete non-human toxicity data (out of 8) on lidocaine, please visit the HSDB record page.

[1]. Setting up for the block: the mechanism underlying lidocaine's use-dependent inhibition of sodium channels. J Physiol. 2007 Jul 1;582(Pt 1):11.

[2]. Lidocaine inhibits growth, migration and invasion of gastric carcinoma cells by up-regulation of miR-145. BMC Cancer. 2019 Mar 15;19(1):233.

[3]. Evaluation of the antinociceptive effects of lidocaine and bupivacaine on the tail nerves of healthy rats. Basic Clin Pharmacol Toxicol. 2013 Jul;113(1):31-6.

Therapeutic Uses
Local anesthetic; antiarrhythmic; voltage-gated sodium channel blocker. Lidocaine hydrochloride is used for infiltration anesthesia and nerve block techniques, including peripheral nerve blocks, sympathetic nerve blocks, epidural (including tail) blocks, and spinal block anesthesia. /Included on US Product Label/ Lidocaine has been administered intraperitoneally for the anesthesia of the peritoneum and pelvic organs. /Not Included on US Product Label/ Lidocaine is considered an alternative antiarrhythmic to amiodarone for the treatment of cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia unresponsive to cardiopulmonary resuscitation (CPR), electrical cardioversion (e.g., after 2 to 3 shocks), and vasopressors (epinephrine, vasopressin). /Included on US Product Label/ For more complete data on the therapeutic uses of lidocaine (21 in total), please visit the HSDB record page.

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Drug Warning
Warning: May cause life-threatening or even fatal events in infants and young children. Post-marketing reports indicate that in children under 3 years of age, failure to strictly adhere to dosage and administration recommendations when using 2% lidocaine viscous solution may result in seizures, cardiopulmonary arrest, and death. Generally, 2% lidocaine viscous solution should not be used during teething pain. In other cases, use of this product in children under 3 years of age should be limited to situations where no safer alternative is available or other alternatives have been tried without success. To reduce the risk of serious adverse events from the use of 2% lidocaine viscous solution, instruct caregivers to strictly adhere to the prescribed dosage and frequency of administration, and keep the prescription vial securely out of the reach of children.
Life-threatening adverse reactions (such as arrhythmia, seizures, dyspnea, coma, death) may occur when a local anesthetic is applied to a large area of skin, the application site is covered with an occlusive dressing, a large amount of local anesthetic is used, an anesthetic is applied to irritated or broken skin, or when skin temperature is elevated (e.g., during exercise or the use of an electric blanket). ^{101 102} When used in this manner, the systemic absorption dose of anesthetic is unpredictable, and the resulting plasma concentrations may be sufficient to cause life-threatening adverse reactions.
The U.S. Food and Drug Administration (FDA) has reviewed reports of 35 patients with chondrolysis (chondrogenesis and destruction of cartilage). Postoperative pain in patients can be managed with continuous intra-articular infusion of local anesthetic via an elastic infusion device. This injury is significant for previously healthy young people and warrants attention from healthcare professionals. Local anesthetics (with or without epinephrine) are infused directly into the joint cavity via an elastic pump over a period of 48 to 72 hours. The median time to diagnosis of chondrolysis is 8.5 months after infusion. Almost all reported cases of chondrolysis (97%) occur after shoulder surgery. Joint pain, stiffness, and limited mobility appear as early as the second month after infusion. More than half of the cases require repeat surgery, including arthroscopic surgery or arthroplasty (joint replacement). The specific factors or combinations of factors contributing to chondrolysis in these cases are currently unknown. Infused local anesthetics, instrument materials, and/or other factors may cause cartilage resorption. Notably, single intra-articular injections of local anesthetics have been used for many years in orthopedic surgery without reported cartilage resorption. Local anesthetics are approved for injection to achieve local or regional anesthesia or analgesia. Neither local anesthetics nor infusion devices are approved for continuous intra-articular infusion. Local anesthetics should only be used by experienced clinicians with the ability to diagnose and manage dose-related toxicities and other acute emergencies associated with such drugs. When using lidocaine, resuscitation equipment, oxygen, medications, and personnel necessary to treat adverse reactions should be readily available. Proper patient positioning is crucial during spinal anesthesia. For more complete data on lidocaine warnings (31 in total), please visit the HSDB record page. Pharmacodynamics: High lidocaine blood concentrations can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. In cases of central nervous system blockade, these changes may be attributed to autonomic nerve fiber blockade, the direct inhibitory effect of local anesthetics on various components of the cardiovascular system, and/or the stimulatory effect of adrenaline (if present) on β-adrenergic receptors. Typically, the net effect, within recommended dose limits, is mild hypotension. In particular, this cardiac effect may be related to the primary action of lidocaine, which binds to and blocks sodium channels, inhibiting the ion flow that initiates and conducts the electrical action potential impulses required for muscle contraction. Subsequently, in cardiomyocytes, lidocaine may block or slow the rise of the myocardial action potential and its associated myocardial cell contraction, leading to adverse reactions such as hypotension, bradycardia, myocardial depression, arrhythmias, and even cardiac arrest or circulatory failure. Furthermore, lidocaine has a dissociation constant (pKa) of 7.7 and is a weak base. Therefore, approximately 25% of lidocaine molecules exist in a non-ionized form at physiological pH 7.4, enabling them to enter nerve cells, meaning that lidocaine has a faster onset of action than other local anesthetics with higher pKa values. Lidocaine takes effect approximately 1 minute after intravenous injection and approximately 15 minutes after intramuscular injection. The injected lidocaine then rapidly diffuses into surrounding tissues. The anesthetic effect lasts approximately 10 to 20 minutes after intravenous injection and approximately 60 to 90 minutes after intramuscular injection. However, inflammation appears to reduce the efficacy of lidocaine. This effect may be due to a decrease in the number of nonionized lidocaine molecules caused by acidosis, leading to a faster decline in lidocaine concentration due to increased blood flow, or it may be due to increased production of inflammatory mediators such as peroxynitrite, which can directly act on sodium channels.

C₁₄H₂₃CLN₂O

270.80

270.149

73-78-9

Lidocaine;137-58-6;Lidocaine-d6 hydrochloride;2517378-96-8;Lidocaine-d10 hydrochloride;1189959-13-4;Lidocaine;137-58-6

3676

White to off-white solid powder

350.8ºC at 760 mmHg

80-82°C

166ºC

3.458

1

2

5

17

228

0

NNJVILVZKWQKPM-UHFFFAOYSA-N

InChI=1S/C14H22N2O/c1-5-16(6-2)10-13(17)15-14-11(3)8-7-9-12(14)4/h7-9H,5-6,10H2,1-4H3,(H,15,17)

2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 100 mg/mL (~369.28 mM)
DMSO : ≥ 100 mg/mL (~369.28 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 120 mg/mL (443.13 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)