Co-Danthramer
Co-Danthramer Uses, Dosage, Side Effects, Food Interaction and all others data.
Withdrawn from the Canadian, US, and UK markets in 1998 due to genotoxicity.
Poloxamer 188 (P188) is a nonionic block linear copolymer that exhibits rheologic, anti-thrombotic, anti-inflammatory, and cytoprotective activities in various tissue injury models . Composed of two hydrophilic side-chains attached to a hydrophobic center core , its average molecular weight is 8400 Daltons. P188 has been approved by the FDA for more than 50 years as a therapeutic agent to reduce viscosity in the blood before transfusions . Due to its sufactant properties, P188 may also be found in over-the-counter (OTC) products such as toothpaste, laxatives and mouthwash, and used in various cosmetic, industrial and pharmaceutical applications. There is an evidence of P188 increasing the structural stability and resealing of the plasma membrane via direct incorporation into the phospholipid bilayer . The ability of P188 in attenuating membrane damage and cell injury has been demonstrated in a variety of in vivo and in vitro models . The use of P188 as a potential treatment in different pathological conditions, such as chronic microvascular diseases and skeletal muscle deficiencies, is under investigation .
Poloxamer 188 (P188) exerts a protective action against oxidative stress and inflammation in tissue injury in various experimental models. In the rat model of excitotoxic injury, immediate intrathecal administration of P188 reduced neuronal loss, indicated by smaller spherical excitotoxic lesions . In a murine hind-limb model, P188 mediated a protective action against ischemia-reperfusion injury as indicated by decreased myocyte injury, preserved tissue adenosine 5'-triphosphate levels, and improved survival rates, suggesting that P188 can seal defects in cell membranes and attenuate damage induced by reactive oxygen species . P188 was shown to elicit protective effects against excitotoxic injury, and trauma-induced necrotic and apoptotic cell death in cultured neurons . In the mouse stroke models, P188 exerted a neuroprotective effect in brain ischemia-reperfusion induced acute injury by significantly reducing infarct volume and water content in brain edema and ameliorating the neurological symptoms 24 h after ischemia or reperfusion injury . P188 also significantly inhibited inflammatory, coagulation, and apoptotic responses resulting from superior mesenteric artery occlusion . In the experimental model of striatum injury in rats, P188 was shown to reduce excitotoxicity-induced tissue loss and macrophage infiltrate .
| Trade Name | Co-Danthramer |
| Generic | poloxamer 188 + dantron |
| Type | oral suspension |
| Therapeutic Class | |
| Manufacturer | Pinewood Healthcare |
| Available Country | United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Dantron is a drug used to relieve acute and chronic inflammation of the oral cavity and oropharynx.
Poloxamer 188 is a medication used to clean wounds.
Indicated to reduce viscosity in the blood before transfusions.
Co-Danthramer is also used to associated treatment for these conditions: Oropharyngeal inflammation
How Co-Danthramer works
P188 seals stable defects in cell membranes induced by skeletal muscle cell membranes rupture induced by ischemia-reperfusion injury, electroporation, irradiation, and heat damage . The full mechanism of action of P188 in inducing cytoprotective effects is not clear; however, based on in vitro experiments and the structural similarity to plasmalemma, P188 may be directly incorporated into the phospholipid bilayer to attenuate the extent of tissue injury . Its high surface activity facilitates P188 to be inserted into lipid monolayers . P188 is proposed to exert localized actions by only interacting with damaged and compromised bilayers where the local lipid packing density is reduced . In addition to the direct interaction with the membrane, P188 was shown to inhibit MMP-9 protein levels and activity, as well as the NF-κB signal pathway, in the model of acute cerebral ischemia, which is associated with increased BBB permeability leading to cerebral edema and increased penetration . MMP-9 is a key factor in extracellular matrix (ECM) degradation and BBB disruption.
Toxicity
In an acute oral toxicity study in rat, the LD50 was 9380 mg/kg . P188 has been demonstrated to be safe when given for up to 72 hours .
Volume of Distribution
The volume of distribution at steady state (Vss) after a continuous intravenous infusion of 500 mg/kg of P188 on day 7 was approximately 2.13 mL/kg in pregnant female rats . Vss was 876 mL/kg in dogs receiving a dose of 720 mg/kg/day .
Elimination Route
Following a 48-hour continuous intravenous infusion of purified P188 in healthy volunteers, the mean concentration of P188 at steady state concentration (Css) was 522 ± 118 mg/L and the maximum concentration occurring at the end of the loading dose was approximately 909 ± 165 mg/L . The plasma concentrations were dose-proportional .
Half Life
In humans, P188 has half-life of 18 hours . The terminal plasma elimination half-life was approximately 7.65 ± 1.10 hours in healthy volunteers receiving a 48-hour continuous intravenous infusion of purified P188 .
Clearance
Following a 48-hour continuous intravenous infusion of purified P188 in healthy volunteers, the mean total body clearance was estimated to be 4.40 ± 0.77 L/h when using the plasma concentration data only . Estimated mean renal clearance from the amount of P-188 excreted in urine was 5.21 ± 1.28 L/h . The clearance of a single metabolite HW1 was slower than the parent compound .
Elimination Route
Renal clearance accounted for 90% of total plasma clearance in healthy male subjects .
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