Chemical formula: C₂₂₁H₃₆₆N₇₂O₆₇S Molecular mass: 5,005.76 g/mol PubChem compound: 56928011
In vitro, tesamorelin binds and stimulates human GRF receptors with similar potency as the endogenous GRF.
Growth hormone-releasing factor (GHRF), also known as growth hormone-releasing hormone (GHRH), is a hypothalamic peptide that acts on the pituitary somatotroph cells to stimulate the synthesis and pulsatile release of endogenous growth hormone (GH), which is both anabolic and lipolytic. GH exerts its effects by interacting with specific receptors on a variety of target cells, including chondrocytes, osteoblasts, myocytes, hepatocytes, and adipocytes, resulting in a host of pharmacodynamic effects. Some, but not all these effects, are primarily mediated by IGF-1 produced in the liver and in peripheral tissues.
Tesamorelin stimulates growth hormone secretion, and subsequently increases IGF-1 and IGFBP-3 levels. No clinically significant changes in the levels of other pituitary hormones, including thyroid-stimulating hormone (TSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH) and prolactin, were observed in patients receiving tesamorelin in clinical trials.
The absolute bioavailability of tesamorelin after subcutaneous administration of a 2 mg dose of tesamorelin (1 mg/vial formulation) was determined to be less than 4% in healthy adult subjects.
Single and multiple dose pharmacokinetics have been characterized in healthy subjects and HIV-infected patients without lipodystrophy using a 2 mg dose of tesamorelin (1 mg/vial formulation). Tesamorelin mean extent of absorption (AUC) was 34% higher in HIV-infected patients than healthy subjects. Tesamorelin peak plasma concentration (Cmax) was similar in HIV-infected patients and healthy subjects. The median peak plasma tesamorelin concentration (Tmax) was 0.15 h in both populations.
Following single dose of subcutaneous administration of 1.4 mg of tesamorelin (2 mg/vial formulation) in healthy subjects, the mean [coefficient of variation (CV)] AUC0-inf was 889.1 (57%) pg.h/mL. The mean (CV) Cmax value was 2956.1 (47%) pg/mL and the median Tmax was 0.15 h.
The systemic exposure (Cmax and AUCs) of tesamorelin is similar between the 1.4 mg dose of tesamorelin (2 mg/vial formulation) and the 2 mg dose of tesamorelin (1 mg/vial formulation).
The mean volume of distribution (±SD) of tesamorelin following a single subcutaneous administration of the 1.4 mg dose of tesamorelin (2 mg/vial formulation) was 4.8 ± 1.9 L/kg in healthy subjects.
No formal metabolism studies have been performed in humans.
Mean elimination half-life (t1/2) of tesamorelin was 8 minutes in healthy subjects after single dose subcutaneous administration of the 1.4 mg of tesamorelin (2 mg/vial formulation).
Pharmacokinetics of tesamorelin in patients with renal or hepatic impairment, in pediatric patients, or in elderly patients has not been established.
The effect of multiple dose administration of tesamorelin on the pharmacokinetics of simvastatin and simvastatin acid was evaluated in healthy subjects. Co-administration with simvastatin (a CYP3A substrate) resulted in 8% decrease in extent of absorption (AUCinf) and 5% increase in rate of absorption (Cmax) of simvastatin. For simvastatin acid there was a 15% decrease in AUCinf and 1% decrease in Cmax.
The effect of multiple dose administration of tesamorelin on the pharmacokinetics of ritonavir was evaluated in healthy subjects. Co-administration with ritonavir resulted in 9% decrease in AUCinf and 11% decrease in Cmax of ritonavir.
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