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治療オプション:
Militian Inessa Mesropovna 、薬局による医学的評価、 最終更新日:16.03.2022
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同じ成分を持つトップ20の薬:
同じ治療法の上位20の薬:
リプリカインクリーム(リドカイン2.5%とプリロカイン2.5%の共融混合物)は、以下で使用するための局所麻酔薬として示されています。
-通常の無傷の皮膚。 局所鎮痛用。.
-性器粘膜。 表面的な軽度の手術および浸潤麻酔の前処理として。.
リプリカイン(リドカインとプリロカイン)クリームは、動物実験で観察された耳毒性の影響により、 ⁇ 膜を超えて中耳に浸透または移行する可能性がある場合、いかなる臨床状況でも推奨されません(参照)。 警告。).
Adult Patients - Intact Skin
A thick layer of Liprikaine (lidocaine and prilocaine) Cream is applied to intact skin and covered with an occlusive dressing (see Instruction For Application).
Minor Dermal Procedures: For minor procedures such as intravenous cannulation and venipuncture, apply 2.5 grams of Liprikaine (lidocaine and prilocaine) Cream (1/2 the 5 g tube) over 20 to 25 cm2 of skin surface for at least 1 hour. In controlled clinical trials using Liprikaine (lidocaine and prilocaine) Cream, two sites were usually prepared in case there was a technical problem with cannulation or venipuncture at the first site.
Major Dermal Procedures: For more painful dermatological procedures involving a larger skin area such as split thickness skin graft harvesting, apply 2 grams of Liprikaine (lidocaine and prilocaine) Cream per 10 cm2 of skin and allow to remain in contact with the skin for at least 2 hours.
Adult Male Genital Skin: As an adjunct prior to local anesthetic infiltration, apply a thick layer of Liprikaine (lidocaine and prilocaine) Cream (1 g/10 cm2) to the skin surface for 15 minutes. Local anesthetic infiltration should be performed immediately after removal of Liprikaine (lidocaine and prilocaine) Cream.
Dermal analgesia can be expected to increase for up to 3 hours under occlusive dressing and persist for 1 to 2 hours after removal of the cream. The amount of lidocaine and prilocaine absorbed during the period of application can be estimated from the information in Table 2, ** footnote, in Individualization of Dose.
Adult Female Patients - Genital Mucous Membranes
For minor procedures on the female external genitalia, such as removal of condylomata acuminata, as well as for use as pretreatment for anesthetic infiltration, apply a thick layer (5-10 grams) of Liprikaine (lidocaine and prilocaine) Cream for 5 to 10 minutes.
a href="/script/main/art.asp?articlekey=24885">Occlusion is not necessary for absorption, but may be helpful to keep the cream in place. Patients should be lying down during the Liprikaine (lidocaine and prilocaine) Cream application, especially if no occlusion is used. The procedure or the local anesthetic infiltration should be performed immediately after the removal of Liprikaine (lidocaine and prilocaine) Cream.
Pediatric Patients - Intact Skin
The following are the maximum recommended doses, application areas and application times for Liprikaine (lidocaine and prilocaine) Cream based on a child's age and weight:
Age and Body Weight Requirements | Maximum Total Dose of Liprikaine Cream | Maximum Application Area | Maximum Application Time |
0 up to 3 months or < 5 kg | 1 g | 10 cm2 | 1 hour |
3 up to 12 months and > 5 kg | 2 g | 20 cm2 | 4 hours |
1 to 6 years and > 10 kg | 10 g | 100 cm2 | 4 hours |
7 to 12 years and > 20 kg | 20 g | 200 cm2 | 4 hours |
Please note: If a patient greater than 3 months old does not meet the minimum weight requirement, the maximum total dose of Liprikaine (lidocaine and prilocaine) Cream should be restricted to that which corresponds to the patient's weight. (see Instruction For Application).
Practitioners should carefully instruct caregivers to avoid application of excessive amounts of Liprikaine Cream (see PRECAUTIONS).
When applying Liprikaine (lidocaine and prilocaine) Cream to the skin of young children, care must be taken to maintain careful observation of the child to prevent accidental ingestion of Liprikaine (lidocaine and prilocaine) Cream or the occlusive dressing. A secondary protective covering to prevent inadvertent disruption of the application site may be useful.
Liprikaine (lidocaine and prilocaine) Cream should not be used in neonates with a gestational age less than 37 weeks nor in infants under the age of 12 months who are receiving treatment with methemoglobin-inducing agents (see Methemoglobinemia subsection of WARNINGS).
When Liprikaine Cream (lidocaine 2.5% and prilocaine 2.5%) is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered (see Individualization of Dose). The amount absorbed in the case of Liprikaine (lidocaine and prilocaine) Cream is determined by the area over which it is applied and the duration of application under occlusion (see Table 2, ** footnote, in Individualization of Dose).
Although the incidence of systemic adverse reactions with Liprikaine (lidocaine and prilocaine) Cream is very low, caution should be exercised, particularly when applying it over large areas and leaving it on for longer than 2 hours. The incidence of systemic adverse reactions can be expected to be directly proportional to the area and time of exposure (see Individualization of Dose).
Instruction For Application
To measure 1 gram of Liprikaine (lidocaine and prilocaine) , the Cream should be gently squeezed out of the tube as a narrow strip that is 1.5 inches (3.8 cm) long and 0.2 inches (5 mm) wide. The strip of Liprikaine (lidocaine and prilocaine) cream should be contained within the lines of the diagram shown below.
≈1 g strip
1.5 X 0.2 inches
Use the number of strips that equals your dose, like the examples in the table below.
Dosing Information
1 gram = 1 strip
2 grams = 2 strips
2.5 grams = 2.5 strips
For adult and pediatric patients, apply ONLY as prescribed by your physician.
If your child is below the age of 3 months or small for their age, please inform your doctor before applying Liprikaine (lidocaine and prilocaine) Cream, which can be harmful, if applied over too much skin at one time in young children.
When applying Liprikaine (lidocaine and prilocaine) to the intact skin of young children, it is important that they be carefully observed by an adult in order to prevent the accidental ingestion of or eye contact with Liprikaine Cream.
Liprikaine® (lidocaine and prilocaine) Cream must be applied to intact skin at least 1 hour before the start of a routine procedure and for 2 hours before the start of a painful procedure. A protective covering of the Cream is not necessary for absorption but may be helpful to keep the cream in place.
If using a protective covering, your doctor will remove it, wipe off the Liprikaine® (lidocaine and prilocaine) Cream, clean the entire area with an antiseptic solution before the procedure. The duration of effective skin anesthesia will be at least 1 hour after removal of the protective covering.
PRECAUTIONS
- Do not apply near eyes or on open wounds.
- Keep out of reach of children.
- If your child becomes very dizzy, excessively sleepy, or develops duskiness of the face or lips after applying Liprikaine (lidocaine and prilocaine) Cream, remove the cream and contact the child's physician at once.
Liprikaine Cream (lidocaine 2.5% and prilocaine 2.5%) is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type or to any other component of the product.
WARNINGS
Application of Liprikaine (lidocaine and prilocaine) Cream to larger areas or for longer times than those recommended could result in sufficient absorption of lidocaine and prilocaine resulting in serious adverse effects (see Individualization of Dose).
Patients treated with class III anti-arrhythmic drugs (eg, amiodarone, bretylium, sotalol, dofetilide) should be under close surveillance and ECG monitoring considered, because cardiac effects may be additive.
Studies in laboratory animals (guinea pigs) have shown that Liprikaine (lidocaine and prilocaine) Cream has an ototoxic effect when instilled into the middle ear. In these same studies, animals exposed to Liprikaine (lidocaine and prilocaine) Cream only in the external auditory canal, showed no abnormality. Liprikaine (lidocaine and prilocaine) Cream should not be used in any clinical situation when its penetration or migration beyond the tympanic membrane into the middle ear is possible.
Methemoglobinemia: Liprikaine (lidocaine and prilocaine) Cream should not be used in those rare patients with congenital or idiopathic methemoglobinemia and in infants under the age of twelve months who are receiving treatment with methemoglobin-inducing agents.
Very young patients or patients with glucose-6-phosphate dehydrogenase deficiencies are more susceptible to methemoglobinemia.
Patients taking drugs associated with drug-induced methemoglobinemia such as sulfonamides, acetaminophen, acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, quinine, are also at greater risk for developing methemoglobinemia.
There have been reports of significant methemoglobinemia (20-30%) in infants and children following excessive applications of Liprikaine (lidocaine and prilocaine) Cream. These cases involved the use of large doses, larger than recommended areas of application, or infants under the age of 3 months who did not have fully mature enzyme systems. In addition, a few of these cases involved the concomitant administration of methemoglobin-inducing agents. Most patients recovered spontaneously after removal of the cream. Treatment with IV methylene blue may be effective if required.
Physicians are cautioned to make sure that parents or other caregivers understand the need for careful application of Liprikaine (lidocaine and prilocaine) Cream, to ensure that the doses and areas of application recommended in Table 2 are not exceeded (especially in children under the age of 3 months) and to limit the period of application to the minimum required to achieve the desired anesthesia.
Neonates and infants up to 3 months of age should be monitored for Met-Hb levels before, during, and after the application of Liprikaine (lidocaine and prilocaine) Cream, provided the test results can be obtained quickly.
PRECAUTIONS
General
Repeated doses of Liprikaine Cream may increase blood levels of lidocaine and prilocaine. Liprikaine (lidocaine and prilocaine) Cream should be used with caution in patients who may be more sensitive to the systemic effects of lidocaine and prilocaine including acutely ill, debilitated, or elderly patients.
Liprikaine (lidocaine and prilocaine) Cream should not be applied to open wounds.
Care should be taken not to allow Liprikaine (lidocaine and prilocaine) Cream to come in contact with the eye because animal studies have demonstrated severe eye irritation. Also the loss of protective reflexes can permit corneal irritation and potential abrasion. Absorption of Liprikaine (lidocaine and prilocaine) Cream in conjunctival tissues has not been determined. If eye contact occurs, immediately wash out the eye with water or saline and protect the eye until sensation returns.
Patients allergic to paraaminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine and/or prilocaine; however, Liprikaine (lidocaine and prilocaine) Cream should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.
Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations of lidocaine and prilocaine.
Lidocaine and prilocaine have been shown to inhibit viral and bacterial growth. The effect of Liprikaine (lidocaine and prilocaine) Cream on intradermal injections of livevaccines has not been determined.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Long-term studies in animals designed to evaluate the carcinogenic potential of lidocaine and prilocaine have not been conducted.
Metabolites of prilocaine have been shown to be carcinogenic in laboratory animals. In the animal studies reported below, doses or blood levels are compared with the Single Dermal Administration (SDA) of 60 g of Liprikaine (lidocaine and prilocaine) Cream to 400 cm2 for 3 hours to a small person (50 kg). The typical application of Liprikaine (lidocaine and prilocaine) Cream for one or two treatments for venipuncture sites (2.5 or 5 g) would be 1/24 or 1/12 of that dose in an adult or about the same mg/kg dose in an infant.
Chronic oral toxicity studies of ortho-toluidine, a metabolite of prilocaine, in mice (450 to 7200 mg/m2; 60 to 960 times SDA) and rats (900 to 4,800 mg/m2; 60 to 320 times SDA) have shown that ortho-toluidine is a carcinogen in both species. The tumors included hepatocarcinomas/adenomas in female mice, multiple occurrences of hemangiosarcomas/hemangiomas in both sexes of mice, sarcomas of multiple organs, transitional-cell carcinomas/papillomas of urinary bladder in both sexes of rats, subcutaneous fibromas/fibrosarcomas and mesotheliomas in male rats, and mammary gland fibroadenomas/adenomas in female rats. The lowest dose tested (450 mg/m2 in mice, 900 mg/m2 in rats, 60 times SDA) was carcinogenic in both species. Thus the no-effect dose must be less than 60 times SDA. The animal studies were conducted at 150 to 2,400 mg/kg in mice and at 150 to 800 mg/kg in rats. The dosages have been converted to mg/m2 for the SDA calculations above.
Mutagenesis: The mutagenic potential of lidocaine HCl has been tested in a bacterial reverse (Ames) assay in Salmonella, an in vitro chromosomal aberration assay using human lymphocytes and in an in vivo micronucleus test in mice. There was no indication of mutagenicity or structural damage to chromosomes in these tests.
Ortho-toluidine, a metabolite of prilocaine, at a concentration of 0.5 µg/mL was genotoxic in Escherichia coliDNA repair and phage-induction assays. Urine concentrates from rats treated with ortho-toluidine (300 mg/kg orally; 300 times SDA) were mutagenic when examined in Salmonella typhimurium in the presence of metabolic activation. Several other tests on ortho-toluidine, including reverse mutations in five different Salmonella typhimurium strains in the presence or absence of metabolic activation and a study to detect single strand breaks in DNA of V79 Chinese hamster cells, were negative.
Impairment of Fertility: See Use in Pregnancy.
Use in Pregnancy: Teratogenic Effects: Pregnancy Category B.
Reproduction studies with lidocaine have been performed in rats and have revealed no evidence of harm to the fetus (30 mg/kg subcutaneously; 22 times SDA). Reproduction studies with prilocaine have been performed in rats and have revealed no evidence of impaired fertility or harm to the fetus (300 mg/kg intramuscularly; 188 times SDA). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Liprikaine (lidocaine and prilocaine) Cream should be used during pregnancy only if clearly needed.
Reproduction studies have been performed in rats receiving subcutaneous administration of an aqueous mixture containing lidocaine HCl and prilocaine HCl at 1:1 (w/w). At 40 mg/kg each, a dose equivalent to 29 times SDA lidocaine and 25 times SDA prilocaine, no teratogenic, embryotoxic or fetotoxic effects were observed.
Labor and Delivery: Neither lidocaine nor prilocaine are contraindicated in labor and delivery. Should Liprikaine (lidocaine and prilocaine) Cream be used concomitantly with other products containing lidocaine and/or prilocaine, cumulative doses from all formulations must be considered.
Nursing Mothers: Lidocaine, and probably prilocaine, are excreted in human milk. Therefore, caution should be exercised when Liprikaine (lidocaine and prilocaine) Cream is administered to a nursing mother since the milk: plasma ratio of lidocaine is 0.4 and is not determined for prilocaine.
Pediatric Use: Controlled studies of Liprikaine (lidocaine and prilocaine) Cream in children under the age of seven years have shown less overall benefit than in older children or adults. These results illustrate the importance of emotional and psychological support of younger children undergoing medical or surgical procedures.
Liprikaine (lidocaine and prilocaine) Cream should be used with care in patients with conditions or therapy associated with methemoglobinemia (see Methemoglobinemia subsection of WARNINGS).
When using Liprikaine (lidocaine and prilocaine) Cream in young children, especially infants under the age of 3 months, care must be taken to insure that the caregiver understands the need to limit the dose and area of application, and to prevent accidental ingestion (see DOSAGE AND ADMINISTRATION and Methemoglobinemia).
In neonates (minimum gestation age: 37 weeks) and children weighing less than 20 kg, the area and duration of application should be limited (see TABLE 2 in Individualization of Dose).
Studies have not demonstrated the efficacy of Liprikaine (lidocaine and prilocaine) Cream for heel lancing in neonates.
Geriatric Use: Of the total number of patients in clinical studies of Liprikaine (lidocaine and prilocaine) Cream, 180 were age 65 to 74 and 138 were 75 and over. No overall differences in safety or efficacy were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Plasma levels of lidocaine and prilocaine in geriatric and non-geriatric patients following application of a thick layer of Liprikaine (lidocaine and prilocaine) Cream are very low and well below potentially toxic levels. However, there are no sufficient data to evaluate quantitative differences in systemic plasma levels of lidocaine and prilocaine between geriatric and non-geriatric patients following application of Liprikaine (lidocaine and prilocaine) Cream.
Consideration should be given for those elderly patients who have enhanced sensitivity to systemic absorption. (See PRECAUTIONS.)
After intravenous dosing, the elimination half-life of lidocaine is significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours). (See CLINICAL PHARMACOLOGY.)
ローカライズされた反応:。 無傷の皮膚にあるリプリカイン(リドカインとプリロカイン)クリームによる治療中または治療直後に、治療部位の皮膚が紅斑または浮腫を発症したり、異常な感覚の遺伝子座になったりすることがあります。. 適用部位での離散性紫斑反応または点状反応のまれなケースが報告されています。. リプリカイン(リドカインとプリロカイン)クリームの使用後の色素沈着過剰のまれなケースが報告されています。. リプリカイン(リドカインとプリロカイン)クリームとの関係または基礎となる手順は確立されていません。. 1,300人を超えるリプリカイン(リドカインおよびプリロカイン)クリーム治療を受けた被験者が関与する無傷の皮膚に関する臨床試験では、そのような局所反応が患者の56%で認められ、一般に軽度で一過性であり、1〜2時間以内に自然に解消しました。. リプリカイン(リドカインとプリロカイン)クリームに起因する深刻な反応はありませんでした。.
最近の2つのレポートは、割礼を受けようとしている新生児の包皮の水ぶくれについて説明しています。. 両方の新生児は、1.0 gのリプリカイン(リドカインとプリロカイン)クリームを受け取りました。.
無傷の皮膚にリプリカイン(リドカインとプリロカイン)クリームで治療された患者では、試験で観察された局所的な影響が含まれます:青白さ( ⁇ 白またはブランチ)37%、発赤(紅斑)30%、温度感覚の変化7%、浮腫6% 、かゆみ2%と発疹、1%未満。.
378人のリプリカイン(リドカインおよびプリロカイン)クリーム治療患者が関与する性器粘膜に関する臨床試験では、患者の41%で1つ以上の塗布部位の反応(通常は軽度で一過性)が認められました。. 最も一般的な塗布部位の反応は、発赤(21%)、 ⁇ 熱感(17%)、浮腫(10%)でした。.
アレルギー反応:。 リドカインまたはプリロカインに関連するアレルギー反応およびアナフィラキシー様反応が発生する可能性があります。. それらはじんま疹、血管性浮腫、気管支 ⁇ 、およびショックによって特徴付けられます。. それらが発生した場合、それらは従来の方法で管理されるべきです。. 皮膚テストによる感度の検出は疑わしい価値があります。.
全身(用量関連)反応:。 リプリカイン(リドカインとプリロカイン)クリームの適切な使用後の全身性の副作用は、吸収される少量が原因である可能性は低いです(参照)。 臨床薬理学の薬物動態サブセクション。)。. リドカインおよび/またはプリロカインの全身性の悪影響は、CNSの興奮および/またはうつ病を含む他のアミド局所麻酔薬で観察されたものと本質的に類似しています。 (立ちくらみ。, 緊張。, 不安。, 陶酔。, 混乱。, めまい。, 眠気。, 耳鳴り。, ぼやけた、または二重視。, ⁇ 吐。, 熱の感覚。, 寒さやしびれ。, けいれん。, 振戦。, けいれん。, 無意識。, 呼吸抑制と逮捕。). 興奮性CNS反応は短い場合もあれば、まったく発生しない場合もあります。その場合、最初の症状は、眠気が無意識に融合する場合があります。. 心血管症状には、徐脈、低血圧、心血管虚脱が起こり、逮捕につながる可能性があります。.
60 g塗布後、血中濃度を400 cmにピークにします。2 無傷の皮膚を3時間使用すると、リドカインは0.05〜0.16 ⁇ µg/ mL、プリロカインは0.02〜0.10 ⁇ µg/ mLになります。. リドカイン(> 5 ⁇ µg/ mL)および/またはプリロカイン(> 6 ⁇ µg/ mL)の毒性レベルは、心臓の出力、全末 ⁇ 抵抗、平均動脈圧の低下を引き起こします。. これらの変化は、これらの局所麻酔薬が心血管系に直接抑制効果をもたらすことが原因である可能性があります。. 大規模な局所的な過剰摂取または経口摂取がない場合、評価には、臨床効果に対する他の病因の評価、またはリドカイン、プリロカインまたは他の局所麻酔薬の他の供給源からの過剰摂取を含める必要があります。. 過剰摂取の管理の詳細については、非経口キシロカイン(リドカインHCl)またはシタネスト(プリロカインHCl)のパッケージ挿入を参照してください。.
Liprikaine Cream is a eutectic mixture of lidocaine 2.5% and prilocaine 2.5% formulated as an oil in water emulsion. In this eutectic mixture, both anesthetics are liquid at room temperature (see DESCRIPTION) and the penetration and subsequent systemic absorption of both prilocaine and lidocaine are enhanced over that which would be seen if each component in crystalline form was applied separately as a 2.5% topical cream.
Absorption: The amount of lidocaine and prilocaine systemically absorbed from Liprikaine (lidocaine and prilocaine) Cream is directly related to both the duration of application and to the area over which it is applied. In two pharmacokinetic studies, 60 g of Liprikaine (lidocaine and prilocaine) Cream (1.5 g lidocaine and 1.5 g prilocaine) was applied to 400 cm2 of intact skin on the lateral thigh and then covered by an occlusive dressing. The subjects were then randomized such that one-half of the subjects had the occlusive dressing and residual cream removed after 3 hours, while the remainder left the dressing in place for 24 hours. The results from these studies are summarized below.
TABLE 1: Absorption of Lidocaine and Prilocaine from Liprikaine (lidocaine and prilocaine) Cream: Normal Volunteers (N=16)
Liprikaine Cream (g) | Area (cm2) | Time on (hrs) | Drug Content (mg) | Absorbed (mg) | Cmax (µg/mL) | Tmax (hr) |
60 | 400 | 3 | lidocaine 1500 | 54 | 0.12 | 4 |
prilocaine 1500 | 92 | 0.07 | 4 | |||
60 | 400 | 24* | lidocaine 1500 | 243 | 0.28 | 10 |
prilocaine 1500 | 503 | 0.14 | 10 | |||
* Maximum recommended duration of exposureis 4 hours. |
When 60 g of Liprikaine (lidocaine and prilocaine) Cream was applied over 400 cm2 for 24 hours, peak blood levels of lidocaine are approximately 1/20 the systemic toxic level. Likewise, the maximum prilocaine level is about 1/36 the toxic level. In a pharmacokinetic study, Liprikaine (lidocaine and prilocaine) Cream was applied to penile skin in 20 adult male patients in doses ranging from 0.5 g to 3.3 g for 15 minutes. Plasma concentrations of lidocaine and prilocaine following Liprikaine (lidocaine and prilocaine) Cream application in this study were consistently low (2.5-16 ng/mL for lidocaine and 2.5-7 ng/mL for prilocaine). The application of Liprikaine (lidocaine and prilocaine) Cream to broken or inflamed skin, or to 2,000 cm2 or more of skin where more of both anesthetics are absorbed, could result in higher plasma levels that could, in susceptible individuals, produce a systemic pharmacologic response.
The absorption of Liprikaine (lidocaine and prilocaine) Cream applied to genital mucous membranes was studied in two open-label clinical trials. Twenty-nine patients received 10 g of Liprikaine (lidocaine and prilocaine) Cream applied for 10 to 60 minutes in the vaginal fornices. Plasma concentrations of lidocaine and prilocaine following Liprikaine (lidocaine and prilocaine) Cream application in these studies ranged from 148 to 641 ng/mL for lidocaine and 40 to 346 ng/mL for prilocaine and time to reach maximum concentration (tmax) ranged from 21 to 125 minutes for lidocaine and from 21 to 95 minutes for prilocaine. These levels are well below the concentrations anticipated to give rise to systemic toxicity (approximately 5000 ng/mL for lidocaine and prilocaine).
Distribution: When each drug is administered intravenously, the steady-state volume of distribution is 1.1 to 2.1 L/kg (mean 1.5, ±0.3 SD, n=13) for lidocaine and is 0.7 to 4.4 L/kg (mean 2.6, ± 1.3 SD, n=13) for prilocaine. The larger distribution volume for prilocaine produces the lower plasma concentrations of prilocaine observed when equal amounts of prilocaine and lidocaine are administered. At concentrations produced by application of Liprikaine (lidocaine and prilocaine) Cream, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 µg/mL of free base) the plasma protein binding of lidocaine is concentration dependent. Prilocaine is 55% bound to plasma proteins. Both lidocaine and prilocaine cross the placental and blood brain barrier, presumably by passive diffusion.
Metabolism: It is not known if lidocaine or prilocaine are metabolized in the skin. Lidocaine is metabolized rapidly by the liver to a number of metabolites including monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity similar to, but less potent than that of lidocaine. The metabolite, 2,6-xylidine, has unknown pharmacologic activity. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine concentrations, respectively. Prilocaine is metabolized in both the liver and kidneys by amidases to various metabolites including ortho-toluidine and N-n-propylalanine. It is not metabolized by plasma esterases. The ortho-toluidine metabolite has been shown to be carcinogenic in several animal models (see Carcinogenesis subsection of PRECAUTIONS). In addition, ortho-toluidine can produce methemoglobinemia following systemic doses of prilocaine approximating 8 mg/kg (see ADVERSE REACTIONS). Very young patients, patients with glucose-6-phosphate dehydrogenase deficiencies and patients taking oxidizing drugs such as antimalarials and sulfonamides are more susceptible to methemoglobinemia (see Methemoglobinemia subsection of PRECAUTIONS).
Elimination: The terminal elimination half-life of lidocaine from the plasma following IV administration is approximately 65 to 150 minutes (mean 110, ±24 SD, n=13). More than 98% of an absorbed dose of lidocaine can be recovered in the urine as metabolites or parent drug. The systemic clearance is 10 to 20 mL/min/kg (mean 13, ±3 SD, n=13). The elimination half-life of prilocaine is approximately 10 to 150 minutes (mean 70, ±48 SD, n=13). The systemic clearance is 18 to 64 mL/min/kg (mean 38, ±15 SD, n=13). During intravenous studies, the elimination half-life of lidocaine was statistically significantly longer in elderly patients (2.5 hours) than in younger patients (1.5 hours). No studies are available on the intravenous pharmacokinetics of prilocaine in elderly patients.
Pediatrics: Some pharmacokinetic (PK) data are available in infants (1 month to < 2 years old) and children (2 to < 12 years old). One PK study was conducted in 9 full-term neonates (mean age: 7 days and mean gestational age: 38.8 weeks). The study results show that neonates had comparable plasma lidocaine and prilocaine concentrations and blood methemoglobin concentrations as those found in previous pediatric PK studies and clinical trials. There was a tendency towards an increase in methemoglobin formation. However, due to assay limitations and very little amount of blood that could be collected from neonates, large variations in the above reported concentrations were found.
Special Populations: No specific PK studies were conducted. The half-life may be increased in cardiac or hepatic dysfunction. Prilocaine's half-life also may be increased in hepatic or renal dysfunction since both of these organs are involved in prilocaine metabolism.