Absorption, Distribution and Excretion
The absolute bioavailability of carisotropium has not been determined. Clinical studies have shown that the mean time to peak plasma concentration (Tmax) is approximately 1.5–2 hours. Concomitant administration of carisotropium (350 mg tablets) with a fatty meal has no effect on its pharmacokinetics. Carisotropium is primarily excreted via the kidneys and other routes. The half-life of meprobamate is approximately 10 hours. Based on four different clinical studies, plasma concentrations ranged from 0.93 to 1.3 L/kg. The oral clearance (Cl/F) after oral administration of carisotropium is 39.52 ± 16.83 L/h. Carisotropium crosses the placenta. The concentration of the drug in breast milk is 2–4 times higher than the maternal plasma concentration. The required plasma concentrations of carisotropium to achieve sedation, skeletal muscle relaxation, or toxicity are currently unknown. One manufacturer reported that after oral administration of 350 mg carisoprodol to healthy adults, plasma concentrations reached 4-7 μg/mL within 4 hours. At commonly used therapeutic doses, the onset of action is typically within 30 minutes, with a duration of action of 4-6 hours. This study aimed to quantify the excretion of carisoprodol and meprobamate in human milk and to estimate the intake dose for breastfed infants. In a woman taking 2100 mg carisoprodol daily, the concentrations of carisoprodol and meprobamate in breast milk were measured under steady-state conditions for four consecutive days. The mean milk concentration of carisoprodol was 0.9 μg/mL, and the mean milk concentration of meprobamate was 11.6 μg/mL. Based on the measured milk concentrations, the absolute intake dose for exclusively breastfed infants was estimated to be 1.9 mg/kg/day, representing a relative dose of 4.1% of the mother's weight-adjusted dose. ...

---

Metabolism/Metabolic Substances
Carlisopredo's primary metabolic pathway involves metabolism in the liver via the cytochrome P450 enzyme CYP2C19 to meprobamate. This enzyme exhibits genetic polymorphism, which may affect the drug's metabolism.
Carlisopredo's primary metabolic pathway involves metabolism in the liver via the cytochrome P450 enzyme CYP2C19 to meprobamate. This enzyme exhibits genetic polymorphism.
Carlisopredo is metabolized in the liver; animal studies have shown that the drug may induce hepatic microsomal enzymes. Animal studies have shown that the drug is primarily excreted in the urine as hydroxycarlisopredo and hydroxymethylprobamate, with a small amount excreted as meprobamate; trace amounts of carlisopredo are excreted unchanged in the urine. The drug can be removed by hemodialysis or peritoneal dialysis.
Carlisopredo is a muscle relaxant and analgesic, and its active metabolite is meprobamate. We conducted an open-label, three-group, single-dose study involving 15 healthy volunteers: 5 with poor mephenytoin metabolism, 5 with poor debromoquine metabolism, and 5 with good metabolism of both substrates. The aim was to investigate whether the clearance of carisotropol and meprobamate depended on two metabolic polymorphisms of mephenytoin and debromoquine, respectively. Subjects received a single oral dose of 700 mg carisotropol and 400 mg meprobamate at different time points. The in vivo distribution of carisotropol significantly correlated with the hydroxylation phenotype of mephenytoin. The mean clearance of carisotropol in the serum of patients with slower mephenytoin metabolism was four times lower than that in those with faster metabolism, confirming our previous hypothesis that N-dealkylation of carisotropol co-segregates with the mephenytoin hydroxylation polymorphism. However, there was no difference in the mean clearance of meprobamate in the serum of the two groups. Furthermore, the polymorphism of deisoquinoline hydroxylation did not affect the clearance of either carisotropol or meprobamate. Therefore, individuals who metabolize mephenytoin more slowly have a lower capacity to metabolize carisotropium, and treatment with standard doses of carisotropium may increase the risk of concentration-dependent side effects such as drowsiness and hypotension. It is metabolized in the liver by the cytochrome P450 oxidase isoenzyme CYP2C19. Elimination pathway: Carisotropium is eliminated via renal and non-renal pathways. Half-life: 8 hours. The terminal half-life is approximately 2 hours. Carisotropium is eliminated via renal and non-renal pathways, with a terminal elimination half-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours. The plasma half-life of carisotropium is approximately 8 hours.

Toxicity Summary
Carlisopredo is a central nervous system depressant with sedative and skeletal muscle relaxant effects. Carlisopredo does not act directly on skeletal muscle, but rather blocks neuronal communication within the reticular formation and spinal cord, thereby producing a sedative effect and altering pain perception. Its exact mechanism of action is not fully understood. Interactions Carlisopredo may have an additive effect of central nervous system depressant effects when used in combination with other central nervous system depressants (including alcohol). Caution should be exercised when carlisopredo is used in combination with other depressants to avoid overdose. Carlisopredo is metabolized in the liver by CYP2C19 to meprobamate. Concomitant use of CYP2C19 inhibitors (such as omeprazole or fluvoxamine) with carlisopredo may result in increased carlisopredo exposure and decreased meprobamate exposure. Concomitant use of CYP2C19 inducers (such as rifampin or St. John's wort) with carlisoplastin may result in decreased carlisoplastin exposure and increased meprobamate exposure. Low-dose aspirin has also been shown to induce CYP2C19. The full pharmacological effect of these potential exposure alterations on the efficacy or safety of carlisoplastin is unclear. Neither carlisoplastin nor tramadol is a federally regulated drug. However, there is evidence that these drugs may have abuse potential, particularly in patients with a history of drug abuse. We report three cases of illicit use of the combination of carlisoplastin and tramadol for psychotropic effects. Carlisoplastin or tramadol should be prescribed with caution in patients at risk of drug abuse; extreme caution should be exercised when prescribing both drugs concurrently in any patient.

Therapeutic Uses
Centrally acting muscle relaxant. Carlisopredo may be used as an adjunct to rest, physical therapy, analgesia, and other measures to relieve discomfort caused by acute painful musculoskeletal disorders. /US product label contains/

---

Drug Warnings Patients may occasionally experience allergic or specific reactions to carlisopredo. In patients who have not previously taken carlisopredo, these reactions usually occur on the fourth dose. Specific reactions may be characterized by extreme weakness, transient quadriplegia, dizziness, ataxia, transient visual loss, diplopia, mydriasis, dysarthria, agitation, euphoria, confusion, and disorientation. These symptoms usually subside within hours; however, some patients may require symptomatic supportive care, including hospitalization. Patients with a history of similar reactions to meprobamate may have experienced rash, erythema multiforme, pruritus, urticaria, eosinophilia, and fixed drug eruption while receiving carlisopredo. Severe allergic reactions are characterized by asthma attacks, fever, fatigue, dizziness, angioedema, eye irritation, hypotension, and anaphylactic shock. The most common adverse reactions to carisotropium are drowsiness and dizziness. Other central nervous system adverse reactions include vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, and insomnia. Because carisotropium is metabolized by the liver and excreted by the kidneys, patients with impaired liver or kidney function should use this drug with caution. Patients should be informed that carisotropium may impair their ability to perform dangerous activities requiring mental alertness or physical coordination, such as operating machinery or driving motor vehicles. Gastrointestinal adverse reactions to carisotropium include nausea, vomiting, hiccups, increased bowel motility, and upper abdominal discomfort. Cardiovascular adverse reactions include tachycardia, orthostatic hypotension, and facial flushing. Although a causal relationship between carisotropium and leukopenia and pancytopenia has not been established, leukopenia and pancytopenia have been rare in patients taking carisotropium concomitantly with other medications. For more complete data on drug warnings for Calisotope (13 in total), please visit the HSDB records page.

---

Pharmacodynamics
Calisopredo is a centrally acting skeletal muscle relaxant. It does not act directly on skeletal muscle but rather on the central nervous system (CNS). This drug relieves pain caused by muscle spasms. Calisotope's metabolite, meprobamate, has both anxiolytic and sedative effects. Clinical studies have shown that this drug can cause impaired psychomotor function in neuropsychological tests.

C12H24N2O4

260.3300

260.173

78-44-4

2576

Crystals

1.1±0.1 g/cm3

423.4±28.0 °C at 760 mmHg

92-92°C

209.9±24.0 °C

0.0±1.0 mmHg at 25°C

1.466

2.15

2

4

9

18

281

0

O(C(N([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])C(C([H])([H])[H])(C([H])([H])OC(N([H])[H])=O)C([H])([H])C([H])([H])C([H])([H])[H]

OFZCIYFFPZCNJE-UHFFFAOYSA-N

InChI=1S/C12H24N2O4/c1-5-6-12(4,7-17-10(13)15)8-18-11(16)14-9(2)3/h9H,5-8H2,1-4H3,(H2,13,15)(H,14,16)

[2-(carbamoyloxymethyl)-2-methylpentyl] N-propan-2-ylcarbamate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

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