As a result, fenofibric acid may accumulate in severe kidney disease ,28,31 and is not eliminated by hemodialysis.31 Since the initial introduction of a fenofibrate in clinical practice, several other formulations have been developed in order to optimize its pharmacologic purchase Temsirolimus properties. The major drawbacks of the original fenofibrate formulation were its low availability and the necessitation of taking it with meals, especially fat meals. The new formulation is Trilipix which is the choline salt of fenofibrate. Trilipix does not require enzymatic cleavage to become active. It rapidly dissociates to the active form of free fenofibric acid within the gastrointestinal tract and does not undergo first-pass hepatic metabolism.21 Trilipix is manufactured as delayed-release 45 mg and 135 mg capsules. The chemical name for choline fenofibrate is ethanaminium, 2-hydroxy-N,N,N-trimethyl, 2-{4- phenoxy] -2-methylpropanoate 32. It is freely soluble in water. Trilipix delayed-release capsules can be taken without regard to meals. Of great importance, fenofibric acid is well absorbed throughout the gastrointestinal tract, and has statistically greater bioavailability than prior fenofibrate formulations, as has been demonstrated in healthy human volunteers.
33 Pharmacokinetics Fenofibric acid Telaprevir clinical trial selleck chemicals is the circulating pharmacologically active moiety in plasma after oral administration of Trilipix. Fenofibric acid is also the circulating pharmacologically active moiety in plasma after oral administration of fenofibrate, the ester of fenofibric acid.
Plasma concentrations of fenofibric acid after one 135 mg delayed-release capsule are equivalent to those after one 200 mg capsule of micronized fenofibrate administered under fed conditions. Absorption Fenofibric acid is well absorbed throughout the gastrointestinal tract. The absolute bioavailability of fenofibric acid is approximately 81%. The absolute bioavailability in the stomach, proximal small bowel, distal small bowel, and colon has been shown to be approximately 81%, 88%, 84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%, respectively, for fenofibrate.33 Fenofibric acid exposure in plasma, as measured by time to peak concentration in plasma and area under the concentration curve , is not significantly different when a single 135 mg dose of Trilipix is administered under fasting or nonfasting conditions.34 Distribution Upon multiple dosing of Trilipix, fenofibric acid levels reach steady state within 8 days.34 Plasma concentrations of fenofibric acid at steady state are approximately slightly more than double those following a single dose. Metabolism Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine.