Target-Mediated Drug Disposition Affects the Pharmacokinetics of Interleukin-10 Fragment Crystallizable Fusion Proteins at Pharmacologically Active Doses.

Animals Half-Life Humans Interleukin-10 / pharmacokinetics Mice Receptors, Interleukin-10 Recombinant Fusion Proteins / pharmacokinetics

Journal

Drug metabolism and disposition: the biological fate of chemicals
ISSN: 1521-009X
Titre abrégé: Drug Metab Dispos
Pays: United States
ID NLM: 9421550

Informations de publication

Date de publication:
07 2022
Historique:
received: 02 12 2021
accepted: 25 04 2022
pubmed: 12 5 2022
medline: 2 7 2022
entrez: 11 5 2022
Statut: ppublish

Résumé

Fragment crystallizable (Fc) fusion is commonly used for extending the half-life of biotherapeutics such as cytokines. In this work, we studied the pharmacokinetics of Fc-fused interleukin-10 (IL-10) proteins that exhibited potent antitumor activity in mouse syngeneic tumor models. At pharmacologically active doses of ≥0.1 mg/kg, both mouse Fc-mouse IL-10 and human Fc-human IL-10, constructed as the C terminus of the Fc domain fused with IL-10 via a glycine-serine polypeptide linker, exhibited nonlinear pharmacokinetics after intravenous administration to mice at the doses of 0.05, 0.5, and 5 mg/kg. With a nominal dose ratio of 1:10:100; the ratio of the area under the curve for mouse Fc-mouse IL-10 and human Fc-human IL-10 was 1:181:1830 and 1:75:633, respectively. In contrast, recombinant mouse or human IL-10 proteins exhibited linear pharmacokinetics in mice. Compartmental analysis, using the Michaelis-Menten equation with the in vitro IL-10 receptor alpha binding affinity inputted as the K

Identifiants

DOI: 10.1124/dmd.121.000799 PMID: 35545256
pubmed: 35545256
pii: dmd.121.000799
doi: 10.1124/dmd.121.000799
doi:

Substances chimiques

Receptors, Interleukin-10 0
Recombinant Fusion Proteins 0
Interleukin-10 130068-27-8

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

898-908

Informations de copyright

Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.

Auteurs

Zheng Yang (Z)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.) yangz@bms.com.

Surendran Rajendran (S)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Vanessa Spires (V)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Brian Poirson (B)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Murali Gururajan (M)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Zheng Lin (Z)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Jaren Arbanas (J)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Stanley Krystek (S)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

James Loy (J)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Yuan Cheng (Y)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Stephen Carl (S)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Samantha Pace (S)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Yun Wang (Y)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

John Mehl (J)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Shihua Xu (S)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Krishna Vasudevan (K)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Miranda Broz (M)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Lois Lehman-McKeeman (L)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Paul Morin (P)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

Robert F Graziano (RF)

Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization (Z.Y.), Nonclinical Disposition and Bioanalysis (S.R., S.X.), Discovery Biotherapeutics (Z.L., J.A., P.M.), Molecular Structure and Design (S.K.), Discovery Pharmaceutics and Analytical Sciences, Pharmaceutical Candidate Optimization (Y.C., S.C., S.P., Y.W., J.M.), Discovery Oncology (V.S., B.P., M.G., R.F.G.), Translational Medicine (K.V.), and Pharmaceutical Candidate Optimization (L.L.-M.), Bristol Myers Squibb, Princeton, New Jersey; Discovery Toxicology, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Cambridge, Massachusetts (J.L.); and Discovery Oncology, Bristol Myers Squibb, Redwood City, California (M.B.).

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Target-Mediated Drug Disposition Affects the...
questionsmedicales.fr › Phénomènes physiques › Temps › Période › Target-Mediated Drug Disposition Affects the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Target-Mediated Drug Disposition Affects the...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-10 › Target-Mediated Drug Disposition Affects the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Target-Mediated Drug Disposition Affects the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux interleukines › Récepteurs à l'interleukine-10 › Target-Mediated Drug Disposition Affects the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › Protéines de fusion recombinantes › Target-Mediated Drug Disposition Affects the...