Linaclotide

Linaclotide is a peptide taken by mouth that acts as an agonist of guanylate cyclase 2C, and it is used to treat irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide made up of fourteen amino acids.

Pharmacodynamics: When Linaclotide was taken straight after a high-fat breakfast, stools were looser and passed more often than when it was taken fasting. In clinical trials, Linaclotide was given on an empty stomach, at least 30 minutes before breakfast.

Pharmacokinetics: Very little Linaclotide is absorbed after an oral dose, so the amount reaching the blood is negligible. Plasma concentrations of Linaclotide and its active metabolite were below the limit of quantitation after oral doses of 145 mcg or 290 mcg. Because of this, standard pharmacokinetic parameters such as the area under the curve (AUC), maximum concentration (Cmax) and half-life (t1/2) cannot be calculated. And since plasma concentrations can't be measured at the recommended oral doses, Linaclotide is not expected to spread into tissues to any clinically relevant extent. Linaclotide is metabolized inside the gastrointestinal tract, where it loses its terminal tyrosine moiety and becomes its principal active metabolite. Both Linaclotide and this metabolite are then broken down by proteolysis in the intestinal lumen into smaller peptides and naturally occurring amino acids. In healthy subjects given Linaclotide 290 mcg once daily for seven days, the active peptide recovered in stool samples averaged about 5% when fasted and about 3% when fed, and all of it was the active metabolite.