Recently Published Publications

Application of an LC–MS/MS method for the simultaneous quantification of human intestinal transporter proteins absolute abundance using a QconCAT technique

Author(s): M.D. Harwood, B. Achour, M.R. Russell, G.L. Carlson, G. Warhurst, A. Rostami-Hodjegan 
Year: 2015

Abstract: Transporter proteins expressed in the gastrointestinal tract play a major role in the oral absorption of some drugs, and their involvement may lead to drug–drug interaction (DDI) susceptibility when given in combination with drugs known to inhibit gut wall transporters. Anticipating such liabilities and predicting the magnitude of the impact of transporter proteins on oral drug absorption and DDIs requires quantification of their expression in human intestine, and linking these to data obtained through in vitro experiments. This study highlights the utility of a QconCAT strategy to quantify absolute transporter abundances in human intestinal tissues.

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Does age affect gastric emptying time? A model-based meta-analysis of data from premature neonates through to adults

Author(s): Jennifer J. Bonner, Pavan Vajjah, Khaled Abduljalil, Masoud Jamei, Amin Rostami-Hodjegan, Geoffrey T. Tucker, Trevor N. Johnson
Year: 2015

Abstract: Gastric emptying (GE) is often reported to be slower and more irregular in premature neonates than in older children and adults. The aim of this study was to investigate the impact of age and other covariates on the rate of GE.

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Population pharmacokinetics and dosing implications for cobimetinib in patients with solid tumors.

Author(s): Han K, Jin JY, Marchand M, Eppler S, Choong N, Hack SP, Tikoo N, Bruno R, Dresser M, Musib L, Budha NR
Year: 2015

Abstract: The purpose of this study was to characterize cobimetinib pharmacokinetics and evaluate impact of clinically relevant covariates on cobimetinib pharmacokinetics. A population pharmacokinetic model was developed for cobimetinib in cancer patients. Covariates had minimal impact on steady-state exposure, suggesting no need for dose adjustments and supporting the recommended dose for all patients.

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Modeling and simulations relating overall survival to tumor growth inhibition in renal cell carcinoma patients.

Author(s): Claret L, Mercier F, Houk BE, Milligan PA, Bruno R.
Year: 2015

Abstract: The purpose of this study was to assess the link between tumor growth inhibition (TGI) and overall survival (OS) based on historical renal cell carcinoma (RCC) data. The published OS model and resultant simulations can be leveraged to support Phase II design and predict expected OS and HR (based on early observed TGI data obtained in Phase II or Phase III studies), thereby informing important mRCC development decisions, e.g., Go/No Go and dose regimen selection.

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Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia.

Author(s): Zhang X, Peyret T, Gosselin NH, Marier JF, Imel EA, Carpenter TO.
Year: 2015

Abstract: X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a novel human anti-FGF23 antibody for the treatment of XLH. The pharmacokinetics (PK) and pharmacodynamics (PD) models of KRN23 were assessed following subcutaneous dosing every 28 days over an initial 4-month dose escalation (0.05-0.6 mg/kg) and a subsequent 12-month titration period (0.1-1.0 mg/kg) in XLH adults.

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