Metabolic manipulator Cerdelga also known as (Eliglustat, Eliglustat tartrate and Genz-112638) belong to class organic (Benzodioxanes)(1). The chemical structure of the Eliglustat (figure.1).(2) Cerdelga medication administered to patient with gaucher disease type 1 who are CYP2D6 extensive metabolisers, intermediate metabolisers or poor metabolisers it is discovered by Sofani clinic and approved by FDA cleared test (3).
Figure 1.The chemical structure of eliglustat.2
Cuase of Goucher disease type 1 due sufficiency of glucocerebrosidase which treated by Cerdelga and depend on genotype for is being treated, CYP2D6 metabolic pathway of Cerdelga engage Sequential oxidation of the octane fragment followed by oxidation of 2,3-dihydro-1,4-benzodioxan.(2) To reduce the fat in the cell that accumulate around the organ(3). Cerdelga (Eliglustat) has strong effect on organ which is fat accumilating in the cell such as ( bone marraw, liver and spleen)(4) Cerdelga treatment to mitigate amount of the fat which is slowing down the formation of the lipid to assist rebalance and clear it.(5)
Mechanic action of Cerdelga (Eliglustat) is glucosylceramide synthase at (IC50 = 10 ng/mL) concentration of inhibitor at 10 ng/mL inhibitor that work as substrate inhibitor of glucosylceramide (1). So after administrating oral Cerdelga medication the absorption in CYP2D6 extensive metabolisers occur at 2 hours to react plasma concentrations, amount elimination after oral administration is Urine (41.8%) and feces (51.4%). Half-life 6.5 hours in (extensive metabolisers) and 8.9 hours (poor metabolisers.)(1) Glucocerebrosidase EC is 126.96.36.199 this is one that is lacking in Gaucher’s disease (1), so it causes by not haven’t enough Beta-glucosidase (EC.188.8.131.52) lysosomal glucocerebrosidase the membrane that linked to the monomeric glycoprotein so this enzyme hydrolyzes beta glucosidic ester bonds and is specialised for lipid substrates. becuase there is not enough enzyme the weekness of its activity results in an accumulation of glucosylceramide, linked by Beta glucosidic bond. Glucosylceramide is located at the end of the glycosphingolipid so it catabolized into ceramide and glucose by glucocerebrosidase(11).like figure 2.
Figure . 2. sufficiency of glucocerebrosidase
which results accumulate fatty (glucocerebroside) in cell(3)
Sanofi Company, Genzyme has been researching for 15 years on treatment for those people who is living with Gaucher Disease and proved by FDA 2014. The treatment was on certain adult patients with the Gaucher disease type 1. Clinical result and approved based on two trail , trail 1 those patient who were new to treatment and trail two the patient switched from enzyme therapy and 400 patient we receiving treatment in 29 country, patient trial one the result was improved seen across (platelet levels, spleen size, liver volume and hemoglobin levels ) within 9 month receiving Cerdelga treatment and for trail two they treated on pre specific criteria for non-interiority due to enzyme replacement therapy also improvement show in following ( platelet levels, spleen size, liver volume and hemoglobin levels ) and the patient continually received Cerdelga treatment over two year . Adverse reaction are (headache, nausea, diarrhea and upper abdominal pain)( 7). Guacher disease is effecting 10,000 people worldwide. The disease causes by not having enough enzyme of beta – glucosidase which responsible for breaking down a specific fat molecule which resulting lipid engorged cell( 7). So the researched investigated and done a deep research. Cerdelga (Eliglustat) is an oral drug contains glucosylceramide which is designed to inhabit the enzyme glucosylceramide synthase the outcome in reduce production of fat that build up on the cell and tissue of patient with Gaucher disease type 1(7) .based on trail one and two EMs and IMs: 84 mg orally twice daily. PMs: 84 mg orally once daily.
Gaucher disease type 1 is lysosomal disorder it is genetic in which deficiency of Glucocerebrosidase GBA gene(3). GBA is enzyme it has important role to breaking down fatty chemical named (glucocerebroside) deficiency of glucocerebrosidase enzyme it won’t break down the fatty properly hence the fatty (glucocerebroside ) accumulate around the organ, this disease has signs and symptoms such as ( Spleen and liver enlargement, low blood count, bruising easily, nose bleeding , bone problem and fatigues)13. doctor needs to order blood test for the patient the test called the beta-glucosidase leukocyte (BGL) to measure the enzymes (glucocerebrosidase) level if the enzymes lever is low it will diagnosis type one Gaucher and treated with Cerdelga (Eliglustat) medication. Cerdelga treatment to mitigate amount of the fat which is slowing down the formation of the lipid to assist rebalance and clear it(13). Cerdelga medication it was first oral treatment made by Sofani Genzyme and it was approved by the U.S Food and Drug Administration (FDA in) 2014(6).
Cerdelga (Eliglustat) tablets are used on long – term treatment basis (1). Cerdelga drug used for long term treatment to reduce the fat in the cell that accumulate around the organ(6) Guacher disease categorised in to three type but Cerdelga prescribed for type 1 Gaucher disease. Cerdelga (Eliglustat) capsule contains 84 mg eliglustat and it is synthetic small molecule white powder it is highly soluble in the water and it is formulated as hard capsule for oral administration (8) Cerdelga (Eliglustat) prescribe and have to supervised by physician to manage Gaucher type 1 ,Note patients Gaucher disease should be genotyped for CYP2D6 to define the CYP2D6 metaboliser status(1). The study has not been done on frequently but recommended dose in CY2D6 PMs 84 mg once a day taken orally and mod-strong CYP3A inhibitor twice a day. Based on physiologically and pharmacokinetic modelling, the systemic exposures in PMs with 84 mg once daily dosing are predicted to be within the range of those observed (1) . Side effect of this drug is considered such as (GI upset , diarrhoea; syncope; headache; arthralgia and fatigue) .Cerdelga can be taken with or without food swallow whole tablet with water (10). This medication interfere with other drug which increase ECG. This disease need to be monitored and blood test and Screen need to be done to check the progression after six months then regularly. (1)
Cerdelga is Oral drug it is belong to class III which needs to be monitered advese effect and to obtain the information that will let the intervention to be use safely(8) . australian Government health Department catagorised all medication in schedual III and A to be cotroled and has restrection on it and all physcian or who work in health care need to folow the policie and procedure(14). However Schedule III drug such as Cerdelga which is controled by Federal Food Drug and Cosmetic Act the medication can not adminstered without any written prescription. Each time persciption have to be perscriped bye healthcare proffesional because cerdelga is long term treatment but every 6 month blood test need to be done for patient with Guacher disease type 1 and closely need to be observed by reffer patient to Screen because Doctor have check to determinde the progression of diorder(6). Important policy regards decumenting this disease and other disease too, all health professional must follow the policy while collecting patients information it is protected by Government and not allow to share with anyone even with family memebrane before taking patient health information have to take the patient consent because all privacy is protected(15