Research ArticleInflammation, Immunopharmacology, and Asthma
Open Access
Translation of Inhaled Drug Optimization Strategies into Clinical Pharmacokinetics and Pharmacodynamics Using GSK2292767A, a Novel Inhaled Phosphoinositide 3-Kinase δ Inhibitor
Malcolm Begg, Chris D. Edwards, J. Nicole Hamblin, Eleni Pefani, Robert Wilson, Jane Gilbert, Giovanni Vitulli, David Mallett, Josie Morrell, Martin I. Hingle, Sorif Uddin, Filzah Ehtesham, Miriam Marotti, Andrew Harrell, Carla F. Newman, Disala Fernando, Jonathan Clark, Anthony Cahn and Edith M. Hessel
Journal of Pharmacology and Experimental Therapeutics June 2019, 369 (3) 443-453; DOI: https://doi.org/10.1124/jpet.119.257311
Malcolm Begg
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Chris D. Edwards
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
J. Nicole Hamblin
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Eleni Pefani
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Robert Wilson
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Jane Gilbert
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Giovanni Vitulli
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
David Mallett
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Josie Morrell
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Martin I. Hingle
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Sorif Uddin
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Filzah Ehtesham
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Miriam Marotti
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Andrew Harrell
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Carla F. Newman
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Disala Fernando
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Jonathan Clark
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Anthony Cahn
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
Edith M. Hessel
Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, United Kingdom (M.B., C.D.E., J.N.H., E.M.H.); Clinical Pharmacology & Model Stimulation, (E.P., R.W.), Drug Metabolism & Pharmacokinetics, (G.V., D.M., J.M.), Refractory Respiratory Inflammation DPU, (S.U.), In Vitro In Vivo Translation, (C.F.N.), Discovery Medicine, (A.C) GlaxoSmithKline, Stevenage, United Kingdom; Global Clinical Science & Delivery, GlaxoSmithKline, Stockley Park, Uxbridge, United Kingdom (M.M., J.G.); In Vitro In Vivo Translation, (A.H.), Drug Product Design & Development, (M.I.H.), GlaxoSmithKline, Ware, United Kingdom (M.I.H.); Department of Biological Chemistry, Babraham Institute, Cambridge, United Kingdom (J.C.); and Clinical Unit Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom (F.E., D.F.)
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In this issue
Research ArticleInflammation, Immunopharmacology, and Asthma
Effective PI3Kδ Inhibitor Optimization and PK/PD Profiles
Malcolm Begg, Chris D. Edwards, J. Nicole Hamblin, Eleni Pefani, Robert Wilson, Jane Gilbert, Giovanni Vitulli, David Mallett, Josie Morrell, Martin I. Hingle, Sorif Uddin, Filzah Ehtesham, Miriam Marotti, Andrew Harrell, Carla F. Newman, Disala Fernando, Jonathan Clark, Anthony Cahn and Edith M. Hessel
Journal of Pharmacology and Experimental Therapeutics June 1, 2019, 369 (3) 443-453; DOI: https://doi.org/10.1124/jpet.119.257311
Research ArticleInflammation, Immunopharmacology, and Asthma
Effective PI3Kδ Inhibitor Optimization and PK/PD Profiles
Malcolm Begg, Chris D. Edwards, J. Nicole Hamblin, Eleni Pefani, Robert Wilson, Jane Gilbert, Giovanni Vitulli, David Mallett, Josie Morrell, Martin I. Hingle, Sorif Uddin, Filzah Ehtesham, Miriam Marotti, Andrew Harrell, Carla F. Newman, Disala Fernando, Jonathan Clark, Anthony Cahn and Edith M. Hessel
Journal of Pharmacology and Experimental Therapeutics June 1, 2019, 369 (3) 443-453; DOI: https://doi.org/10.1124/jpet.119.257311
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