Baricitinib

Baricitinib

· Baricitinib, sold under the brand name Olumiant among others, is a drug for the treatment of rheumatoid arthritis (RA) in adults whose disease was not well controlled using RA medications called tumor necrosis factor (TNF) antagonists.

· It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.The drug is approved for use in the European Union and the United States.

Mechanism

· Baricitinib is a Janus kinase (JAK) inhibitor that reversibly inhibits Janus kinase 1 with a half maximal inhibitory concentration (IC50) of 5.9 nM and Janus kinase 2 with an IC50 of 5.7 nM. Tyrosine kinase 2, which belongs to the same enzyme family, is affected less (IC50 = 53 nM), and Janus kinase 3 far less (IC50 > 400 nM).

· Via a signal transduction pathway involving STAT proteins, this ultimately modulates gene expression in immunological cells.

Pharmacokinetic

· The substance is quickly absorbed from the gut with an absolute bioavailability of 79%. It reaches highest blood plasma levels after about an hour; in different individuals the time to reach this level ranges from 0.5 to 3 hours.

· Food intake has no relevant influence on the drug's pharmacokinetics. 50% of the circulating baricitinib are bound to blood plasma proteins.

· Less than 10% of the substance is metabolized to four different oxidation products by CYP3A4; the rest is left unchanged. Elimination half-life is 12.5 hours on average. About 75% is eliminated via the urine, and 20% via the faeces.

Contraindication

· During pregnancy, the use of baricitinib is contraindicated.

Side Effects

· In studies, upper respiratory tract infections and high blood cholesterol levels (hypercholesterolemia) occurred in more than 10% of patients.

· Less common side effects included other infections such as herpes zoster, herpes simplex, urinary tract infections, and gastroenteritis.

Interactions

· Being metabolized only to a small extent, the substance has a low potential for interactions. In studies, inhibitors of the liver enzymes CYP3A4, CYP2C19, and CYP2C9, as well as the CYP3A4 inducer rifampicin, had no relevant influence on baricitinib concentrations in the bloodstream.

· While baricitinib blocks a number of transporter proteins in vitro, clinically relevant interactions via this mechanism are considered very unlikely, except perhaps for the cation transporter SLC22A1 (OCT1).

References

1. “Baricitinib (Olumiant) Use During Pregnancy". Drugs.com. 8 November 2019. Retrieved 16 March 2020.

2. “Drug Trials Snapshots: Olumiant". U.S. Food and Drug Administration (FDA). 31 May 2018. Retrieved 16 March 2020. This article incorporates text from this source, which is in the public domain.