部份中文美他沙酮处方资料（仅供参考）
英文药名: Skelaxin(Metaxalone Tablets)
中文药名: 美他沙酮片
药品名称
美他沙酮（间恶酮，间沙龙）Metaxalone(Metaxolone)
药理作用
本品为中枢性肌肉松弛药，可阻断脊髓多突触通路，具有镇静作用，也具有抗胆碱和解热镇痛作用。美他沙酮药动学
美他沙酮口服给药后在Beagle犬体内的主要药物动力学参数如下：t1/2为(4.02±3.04)h，tmax为(1.5±0.35)h。pmax为(1 402.31±653.96)mg.L，AUC(0→24)为(2 735.72±1 264.67)mg.L，AUC(0→∞)为(3 109.72±1 283.57)mg.L。
适应症
临床主要用作炎症、外伤等引起的局部肌肉痉挛性疼痛的辅助用药。
用法用量
口服：成人，0.8g，3-4次/天
不良反应
1、常见的不良反应有暑睡、厌食、恶心、呕吐、头晕、口干、尿潴留、贫血及黄疸，严重者可出现脓尿及肾结石。
2、服用本品期间避免进行注意力须高度集中的活动如驾驶、登高、操作精密仪器等。
3、妊娠、哺乳妇女、儿童及肝功能不全者慎用。
4、本品可干扰铜法尿糖的测定结果。
SKELAXIN(Metaxalone)Tablets
Description
SKELAXIN® (metaxalone) is available as an 800 mg oval, scored pink tablet.
Chemically, metaxalone is 5-[(3,5- dimethylphenoxy) methyl]-2-oxazolidinone. The empirical formula is C12H15NO3, which corresponds to a molecular weight of 221.25. The structural formula is:
Metaxalone is a white to almost white, odorless crystalline powder freely soluble in chloroform, soluble in methanol and in 96% ethanol, but practically insoluble in ether or water.
Each tablet contains 800 mg metaxalone and the following inactive ingredients: alginic acid, ammonium calcium alginate, B-Rose Liquid, corn starch and magnesium stearate.
Clinical Pharmacology
Mechanism of Action
The mechanism of action of metaxalone in humans has not been established, but may be due to general central nervous system depression. Metaxalone has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.
Pharmacokinetics
The pharmacokinetics of metaxalone have been eva luated in healthy adult volunteers after single dose administration of SKELAXIN under fasted and fed conditions at doses ranging from 400 mg to 800 mg.
Absorption
Peak plasma concentrations of metaxalone occur approximately 3 hours after a 400 mg oral dose under fasted conditions. Thereafter, metaxalone concentrations decline log-linearly with a terminal half-life of 9.0 ± 4.8 hours. Doubling the dose of SKELAXIN from 400 mg to 800 mg results in a roughly proportional increase in metaxalone exposure as indicated by peak plasma concentrations (Cmax) and area under the curve (AUC). Dose proportionality at doses above 800 mg has not been studied. The absolute bioavailability of metaxalone is not known.
The single-dose pharmacokinetic parameters of metaxalone in two groups of healthy volunteers are shown in Table 1.
Table 1: Mean (%CV) Metaxalone Pharmacokinetic Parameters
Dose (mg) Cmax (ng/mL) Tmax (h) AUC∞ (ng•h/mL) t½(h) CL/F (L/h)
4001 983 (53) 3.3 (35) 7479 (51) 9.0 (53) 68 (50)
8002 1816 (43) 3.0 (39) 15044 (46) 8.0 (58) 66 (51)
1Subjects received 1x400 mg tablet under fasted conditions (N=42)
2Subjects received 2x400 mg tablets under fasted conditions (N=59)
Food Effects
A randomized, two-way, crossover study was conducted in 42 healthy volunteers (31 males, 11 females) administered one 400 mg SKELAXIN tablet under fasted conditions and following a standard high-fat breakfast. Subjects ranged in age from 18 to 48 years (mean age = 23.5 ± 5.7 years). Compared to fasted conditions, the presence of a high fat meal at the time of drug administration increased Cmax by 177.5% and increased AUC (AUC0-t, AUC∞) by 123.5% and 115.4%, respectively. Time-to-peak concentration (Tmax) was also delayed (4.3 h versus 3.3 h) and terminal half-life was decreased (2.4 h versus 9.0 h) under fed conditions compared to fasted.
In a second food effect study of similar design, two 400 mg SKELAXIN tablets (800 mg) were administered to healthy volunteers (N=59, 37 males, 22 females), ranging in age from 18-50 years (mean age = 25.6± 8.7 years). Compared to fasted conditions, the presence of a high fat meal at the time of drug administration increased Cmax by 193.6% and increased AUC (AUC0-t, AUC∞) by 146.4% and 142.2%, respectively. Time-to-peak concentration (Tmax) was also delayed (4.9 h versus 3.0 h) and terminal half-life was decreased (4.2 h versus 8.0 h) under fed conditions compared to fasted conditions. Similar food effect results were observed in the above study when one SKELAXIN 800 mg tablet was administered in place of two SKELAXIN 400 mg tablets. The increase in metaxalone exposure coinciding with a reduction in half-life may be attributed to more complete absorption of metaxalone in the presence of a high fat meal (Figure 1).
Table
Distribution, Metabolism, and Excretion
Although plasma protein binding and absolute bioavailability of metaxalone are not known, the apparent volume of distribution (V/F ~ 800 L) and lipophilicity (log P = 2.42) of metaxalone suggest that the drug is extensively distributed in the tissues. Metaxalone is metabolized by the liver and excreted in the urine as unidentified metabolites.
Pharmacokinetics in Special Populations
Age:
The effects of age on the pharmacokinetics of metaxalone were determined following single administration of two 400 mg tablets (800 mg) under fasted and fed conditions. The results were analyzed separately, as well as in combination with the results from three other studies. Using the combined data, the results indicate that the pharmacokinetics of metaxalone are significantly more affected by age under fasted conditions than under fed conditions, with bioavailability under fasted conditions increasing with age.
Gender:
The effect of gender on the pharmacokinetics of metaxalone was assessed in an open label study, in which 48 healthy adult volunteers (24 males, 24 females) were administered two SKELAXIN 400 mg tablets (800 mg) under fasted conditions. The bioavailability of metaxalone was significantly higher in females compared to males as evidenced by Cmax (2115 ng/mL versus 1335 ng/mL) and AUC∞ (17884 ng·h/mL versus 10328 ng·h/mL). The mean half-life was 11.1 hours in females and 7.6 hours in males. The apparent volume of distribution of metaxalone was approximately 22% higher in males than in females, but not significantly different when adjusted for body weight. Similar findings were also seen when the previously described combined dataset was used in the analysis.
Hepatic/Renal Insufficiency:
The impact of hepatic and renal disease on the pharmacokinetics of metaxalone has not been determined. In the absence of such information, SKELAXIN should be used with caution in patients with hepatic and/or renal impairment.
Indications and Usage
SKELAXIN (metaxalone) is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Metaxalone does not directly relax tense skeletal muscles in man.
Contraindications
Known hypersensitivity to any components of this product.
Known tendency to drug induced, hemolytic, or other anemias.
Significantly impaired renal or hepatic function.
Warnings
SKELAXIN may enhance the effects of alcohol and other CNS depressants.
Precautions
Metaxalone should be administered with great care to patients with pre-existing liver damage. Serial liver function studies should be performed in these patients.
False-positive Benedict’s tests, due to an unknown reducing substance, have been noted. A glucose-specific test will differentiate findings.
Taking SKELAXIN with food may enhance general CNS depression; elderly patients may be especially susceptible to this CNS effect. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and PRECAUTIONS: Information for Patients).
Information for Patients
SKELAXIN may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle, especially when used with alcohol or other CNS depressants.
Drug Interactions
SKELAXIN may enhance the effects of alcohol, barbiturates and other CNS depressants.
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of metaxalone has not been determined.
Pregnancy
Reproduction studies in rats have not revealed evidence of impaired fertility or harm to the fetus due to metaxalone. Post marketing experience has not revealed evidence of fetal injury, but such experience cannot exclude the possibility of infrequent or subtle damage to the human fetus. Safe use of metaxalone has not been established with regard to possible adverse effects upon fetal development. Therefore, metaxalone tablets should not be used in women who are or may become pregnant and particularly during early pregnancy unless in the judgement of the physician the potential benefits outweigh the possible hazards.
Nursing Mothers
It is not known whether this drug is secreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.
Pediatric Use
Safety and effectiveness in children 12 years of age and below have not been established.
Adverse Reactions
The most frequent reactions to metaxalone include:
CNS: drowsiness, dizziness, headache, and nervousness or “irritability”;
Digestive: nausea, vomiting, gastrointestinal upset.
Other adverse reactions are:
Immune System: hypersensitivity reaction, rash with or without pruritus;
Hematologic: leukopenia; hemolytic anemia;
Hepatobiliary: jaundice.
Though rare, anaphylactoid reactions have been reported with metaxalone.
Overdosage
Deaths by deliberate or accidental overdose have occurred with metaxalone, particularly in combination with antidepressants, and have been reported with this class of drug in combination with alcohol.
When determining the LD50 in rats and mice, progressive sedation, hypnosis and finally respiratory failure were noted as the dosage increased. In dogs, no LD50 could be determined as the higher doses produced an emetic action in 15 to 30 minutes.
Treatment - Gastric lavage and supportive therapy. Consultation with a regional poison control center is recommended.
Dosage and Administration
The recommended dose for adults and children over 12 years of age is one 800 mg tablet three to four times a day.
Store at Controlled Room Temperature, between 15°C and 30°C (59°F and 86°F).