Ertugliflozin

Absorption

After administering single doses of 5 mg and 15 mg ertugliflozin under fasted conditions, the median Tmax was one hour. Plasma Cmax and AUC of ertugliflozin increase dose-proportionally. Following administration of a 15 mg dose, the Cmax was 268 ng/mL and the AUC was 1193 ng h/mL. The absolute oral bioavailability of ertugliflozin following administration of a 15 mg dose was approximately 100%, though it is reported to range from 70% to 90%.
Administration of ertugliflozin with a high-fat and high-calorie meal decreases ertugliflozin Cmax by 29%. It prolongs Tmax by one hour but does not alter AUC compared to the fasted state. The observed effect of food on ertugliflozin pharmacokinetics is not considered clinically relevant, and ertugliflozin may be administered with or without food.

Toxicity

The oral LD50 is 500 mg/kg in rats. There are limited clinical experiences of ertugliflozin overdose. It is recommended to initiate supportive measures in the event of drug overdosage. Removal of ertugliflozin by hemodialysis has not been studied.

The Uses of Ertugliflozin

Ertugliflozin is a sodium/glucose cotransporter 2 (SGLT2) inhibitor used to treat type 2 diabetes.

Background

Ertugliflozin is a sodium-dependent glucose cotransporter-2 (SGLT2) inhibitor used to treat type II diabetes mellitus. It works to block glucose reabsorption from the glomerulus.
Ertugliflozin was first approved by the FDA in December 2017. It was also approved by the European Commission in March 2018.

Indications

Ertugliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus (T2DM). It is also available in combination with either metformin or sitagliptin.
Ertugliflozin is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.

Definition

ChEBI: Ertugliflozin is a diarylmethane.

Pharmacokinetics

Ertugliflozin causes a dose-dependent increase in urinary glucose excretion and an increase in urinary volume in patients with T2DM.

Metabolism

Ertugliflozin mainly undergoes O-glucuronidation mediated by UGT1A9 and UGT2B7 to form two pharmacologically inactive glucuronides. About 12% of the drug undergoes CYP-mediated oxidative metabolism. Several metabolites have been found in plasma, feces, and urine. In plasma, the unchanged form of ertugliflozin was found to be the major component of the administered dose.