Relugolix

Relugolix is a non-peptide small molecule and a GnRH receptor antagonist. It binds competitively to the GnRH receptors in the pituitary, so less luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is released, and testosterone falls as a result.

Absorption: Relugolix is a substrate for intestinal P-gp. Its mean (CV%) absolute bioavailability is approximately 12%, and the median (range) Tmax is 2.25 hours.

Effect of food: No clinically meaningful differences in the pharmacokinetics of Relugolix were seen after a high-calorie, high-fat meal.

Distribution: Plasma protein binding is 68 to 71%. Most of it is to albumin and a smaller part is to α1-acid glycoprotein. The mean blood-to-plasma ratio is 0.78.

Elimination: The mean effective half-life is 25 hours, and the mean (CV %) terminal elimination half-life is 60.8 (11%) hours. Mean (CV %) total clearance is 29.4 (15%) L/h, and renal clearance is 8 L/h.

Metabolism: In vitro, Relugolix is metabolized mainly by CYP3A and, to a lesser extent, by CYP2C8.

Excretion: After a single oral 80mg radiolabeled dose, approximately 81% of the radioactivity was recovered in feces (4.2% as unchanged drug) and 4.1% in urine (2.2% as unchanged drug).