Absolute and Relative Bioavailability of Oral Solid Dosage Formulations of Deucravacitinib in Humans. 2023

Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
Bristol Myers Squibb, Princeton, NJ, USA.

Deucravacitinib is an oral, selective, allosteric inhibitor of tyrosine kinase 2, an intracellular signaling kinase involved in the pathogenesis of immune-mediated inflammatory diseases. The absolute and relative bioavailability (BA) were evaluated in phase 1, open-label studies in healthy adults to assess (1) the absolute BA of the deucravacitinib tablet formulation following single oral administration of a 12-mg tablet and an intravenous microdose infusion of 0.1-mg carbon-13 and nitrogen-15-labeled deucravacitinib ([13 C2 , 15 N3 ] deucravacitinib) solution in 8 subjects, and (2) the relative oral BA of deucravacitinib tablet and capsule formulations at the 3- and 12-mg dose levels in 20 subjects. The absolute oral availability of deucravacitinib in the tablet formulation was near complete at approximately 99%. The total clearance (254 mL/min) was low relative to hepatic blood flow, and volume of distribution (∼140 L) was greater than total body water, indicating extravascular distribution. Deucravacitinib systemic exposure (maximum plasma concentration, area under the plasma drug concentration curve from time zero to the time of the last quantifiable nonzero concentration, and area under the plasma drug concentration-time curve from time zero extrapolated to infinity) after administration of the tablet formulation were similar to the capsule at the tested 3- and 12-mg doses. In both studies, deucravacitinib was safe with no clinically relevant changes in laboratory values, electrocardiogram parameters, or vital signs.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D013607 Tablets Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed) Tablet

Related Publications

Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
September 1982, Journal of pharmaceutical sciences,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
August 1983, Journal of pharmaceutical sciences,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
January 1982, Arzneimittel-Forschung,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
September 1994, Arzneimittel-Forschung,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
January 1992, Clinical therapeutics,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
May 1992, Antimicrobial agents and chemotherapy,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
July 1987, International journal of clinical pharmacology, therapy, and toxicology,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
July 2015, Clinical pharmacology in drug development,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
September 1992, Journal of clinical pharmacology,
Anjaneya Chimalakonda, and Wenying Li, and David Marchisin, and Bing He, and Shalabh Singhal, and Prashant Deshpande, and Jonathan Brown, and Urvi Aras, and Bindu Murthy
August 1999, Pharmacotherapy,
Copied contents to your clipboard!