Name | Tesamorelin (usan) |
Synonyms | D06655 TesamorelinAcetate Tesamorelin (usan) TIANFUCHEM--218949-48-5---Tesamorelin (usan) |
CAS | 218949-48-5 |
EINECS | 603-809-2 |
Overview | the 44-amino acid sequence of human growth hormone releasing factor (GRF), A 3-hexenoyl group is attached to the N-terminal residue of its tyrosine with the molecular formula C221H366N72O67S.xC2H4O(x≈ 7), relative molecular mass (free base) 5135.9. It is a novel growth hormone releasing factor analog, which can not only normalize the secretion of growth hormone in the body, but also reduce the increased visceral adipose tissue (VAT), and can improve dyslipidemia and quality of life, maintain glucose homeostasis. The drug was approved by the US FDA in November 2010 for the treatment of HIV-related lipodystrophy syndrome. Figure 1 chemical formula |
pharmacological action | timorelin is a synthetic analog of growth hormone releasing factor (GRF). Similar to the endogenous GRF effect, it acts in vitro by binding to and activating the GRF receptor. GRF is a hypothalamic regulatory polypeptide that stimulates the pituitary growth hormone cells to synthesize and release endogenous growth hormone (GH). GH exerts its pharmacological effects by interacting with specific receptors of target cells including chondrocytes, osteoblasts, cardiomyocytes, hepatocytes and adipocytes. |
pharmacokinetic characteristics | The Absolute bioavailability was less than 4% after subcutaneous injection of 2mg of temorelin in healthy adults. After a single subcutaneous dose of 2mg in healthy people without lipodystrophy and HIV-infected patients, the area under the curve (AUC) was (634.6±72.4) and (852.8±91.9)pghmL-1, respectively, peak plasma concentration (cmax) were (2874.6±43.9) and (2822.3±48.9)pgmL-1, the peak were 1.5h, apparent volume of distribution were (9.4±3.1) and (10.5±6.1)Lkg- 1, the mean elimination half-lives (t1/2) after 14 days of continuous application were 26 and 38min, respectively. |
indication | for the treatment of excessive abdominal fat in HIV-infected patients with lipodystrophy, not recommended for weight loss. The overview, pharmacological effects, indications, and adverse reactions of timorelin were compiled by Oriental editor. (2015-11-23) |
dosage | the recommended dose is 2mg subcutaneously, once a day. The recommended injection site was abdomen. Reconstitution should be carried out according to the instructions before use, and should be discarded if it is not used in time after reconstitution. It should not be frozen or stored in the refrigerator. The reconstituted solution should be clear, colorless and free of visible particles. |
adverse reactions | common adverse reactions are growth hormone effects (eg, Arthralgia, peripheral edema, hyperglycemia) caused by allergic reactions such as rash and urticaria, injection site may appear erythema, itching, pain, urticaria and bleeding. In order to reduce the incidence of adverse reactions at the injection site, it is recommended to shift the injection area in the abdomen. |
contraindications and precautions | , patients with pituitary tumors and other causes of destruction of the hypothalamic-pituitary axis, patients with active malignancies and patients with allergies to the drug. Increased risk of cancer development prior to treatment with temorelin should be carefully considered to increase the risk of malignancy in HIV-positive patients. For patients without a history of malignancy, the benefit of treatment should be carefully assessed before applying the drug; For patients with a history of cure for stable malignancy, the drug should be applied only if the benefits of treatment and the risk of activating a potential malignancy are carefully assessed. 2. Increased IGF-I levels, timerelin can increase GH secretion and serum IGF-I levels. The role of elevated IGF-I levels in malignant tumor progression is unknown. IGF-Ⅰ levels should be closely monitored during treatment. If the patient's IGF-I level continues to increase (eg,> 3SDS), especially in the case of poor efficacy (rate of change of visceral adipose tissue measured by CT scan), the drug should be discontinued. 3. Fluid retention may occur during treatment with temorelin, which is related to the induction of GH secretion, manifested as tissue filling, skeletal muscle discomfort, and lead to various adverse reactions such as edema, arthralgia and carpal tunnel syndrome, can be immediately eliminated after discontinuation. Possible glucose intolerance. Before the application of this product should be carefully assessed glucose status, glucose metabolism should be regularly checked to diagnose glucose intolerance or diabetes. Glucose intolerance can increase the risk of diabetes. Patients whose reduction in visceral adipose tissue, as measured by waist circumference or CT scan, indicates no significant therapeutic effect should be discontinued. Since temorelin can increase IGF-I levels, blood glucose should be monitored regularly. Diabetic patients may aggravate retinopathy after long-term medication. 5. Anaphylactic reaction the patient may present with pruritus, erythema, flushing and urticaria after taking temorelin, which needs symptomatic treatment and drug withdrawal. 6. Study of caution in acute critically ill patients without temorelin. However, it is reported that the use of pharmacological doses of GH can be increased by Mortality Rate after complications in acute critical patients such as open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure. As the drug promotes GH secretion, it should be considered for discontinuation. |
drug interaction | 1. When the drug of CYP450 enzyme-mediated metabolism is combined with the CYP3A4 enzyme substrate simvastatin, the pharmacokinetic characteristics of the drug in healthy people are not significantly affected, indicating that the drug may not affect the activity of CYP3A. The interaction of the drug with other CYP450 isoenzymes has not been evaluated. Studies have shown that GH can regulate the clearance of antipyrine by CYP450, suggesting that GH may alter CYP450 enzyme-mediated metabolism of drugs [such as steroids (including sex hormones), anticonvulsants, clearance of ciclosporin]. Since timerelin promotes GH secretion, its combination with other drugs metabolized by CYP450 enzymes should be closely monitored. 2.11 β-hydroxysteroid dehydrogenase type I (11 β HSD-I) cortisone and prednisone are converted to active metabolites by 11 β HSD-I, and GH inhibits 11 β HSD-I activity. Since timerelin promotes GH secretion, maintenance doses of glucocorticoid replacement therapy should be increased at the start of adrenalectomy. |