Fenofibrate is a third-generation fabric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; to increase high-density lipoprotein cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia, and to reduce triglycerides in patients with severe hypertriglyceridemia[1].

Choline fenofibrate is a newly developed choline salt of fenofibric acid and is more hydrophilic than fenofibrate. It does not require first-pass hepatic metabolism to become active, as it dissociates to free fenofibric acid within the gastrointestinal tract and is rapidly absorbed throughout the gastrointestinal tract. Of the various fenofibrate formulations available, choline fenofibrate is the only formulation approved by the US FDA for co-administration with statins.

To estimate the absolute oral bioavailability of fenofibric acid and choline fenofibrate, a novel and sensitive UPLC–MS/MS method with liquid–liquid extraction procedure was developed to determine fenofibric acid in rat plasma. The separation was achieved on a Phenomenex Kinetex C18 column (50?×?2.1?mm, 2.6?μm) containing 2?mm ammonium acetate–methanol with a gradient elution program. Validations of this method include specificity, sensitivity (limit of quantification, 5?ng/mL), linearity (0.005–10?μg/mL), accuracy (within ±4.3%), precision (intra- and inter-day coefficient of variation <11.3%), recovery (94.9–105.2% for fenofibric acid), matrix effect, stability and dilution, were all within acceptable limits. This method successfully supported the determination of fenofibric acid and choline fenofibrate. The absolute oral bioavailability was 93.4% for choline fenofibrate and 40.0% for fenofibric acid[2]. These results suggested that choline fenofibrate and fenofibric acid had better in vivo pharmacokinetic behaviour than fenofibrate. The two new orally administrated pharmaceuticals, fenofibric acid and choline fenofibrate can be developed as alternatives to fenofibrate.

References

[1] Hua Ling, Daniel Hilleman, John T Luoma. “A Review of Currently Available Fenofibrate and Fenofibric Acid Formulations.” Accounts of Chemical Research 4 2 (2013): 47–55.

[2] Xudan Wei. “Absolute oral bioavailability of fenofibric acid and choline fenofibrate in rats determined by ultra-performance liquid chromatography tandem mass spectrometry.” Biomedical Chromatography 31 4 (2017).