Evaluating drug interaction potential from cytokine release syndrome using a physiologically based pharmacokinetic model: A case study of teclistamab.

Autor: Willemin ME; Janssen Research & Development, Beerse, Belgium., Wang Lin SX; Janssen Research & Development, Spring House, Pennsylvania, USA., De Zwart L; Janssen Research & Development, Beerse, Belgium., Wu LS; Janssen Research & Development, South San Francisco, California, USA., Miao X; Janssen Research & Development, Spring House, Pennsylvania, USA., Verona R; Janssen Research & Development, Spring House, Pennsylvania, USA., Banerjee A; Janssen Research & Development, Spring House, Pennsylvania, USA., Liu B; Janssen Research & Development, Raritan, New Jersey, USA., Kobos R; Janssen Research & Development, Raritan, New Jersey, USA., Qi M; Janssen Research & Development, Raritan, New Jersey, USA., Ouellet D; Janssen Research & Development, Spring House, Pennsylvania, USA., Goldberg JD; Janssen Research & Development, Raritan, New Jersey, USA., Girgis S; Janssen Research & Development, Spring House, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2024 Jul; Vol. 13 (7), pp. 1117-1129. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1002/psp4.13144
Abstrakt: Cytokine release syndrome (CRS) was associated with teclistamab treatment in the phase I/II MajesTEC-1 study. Cytokines, especially interleukin (IL)-6, are known suppressors of cytochrome P450 (CYP) enzymes' activity. A physiologically based pharmacokinetic model evaluated the impact of IL-6 serum levels on exposure of substrates of various CYP enzymes (1A2, 2C9, 2C19, 3A4, 3A5). Two IL-6 kinetics profiles were assessed, the mean IL-6 profile with a maximum concentration (C max ) of IL-6 (21 pg/mL) and the IL-6 profile of the patient presenting the highest IL-6 C max (288 pg/mL) among patients receiving the recommended phase II dose of teclistamab in MajesTEC-1. For the mean IL-6 kinetics profile, teclistamab was predicted to result in a limited change in exposure of CYP substrates (area under the curve [AUC] mean ratio 0.87-1.20). For the maximum IL-6 kinetics profile, the impact on omeprazole, simvastatin, midazolam, and cyclosporine exposure was weak to moderate (mean AUC ratios 1.90-2.23), and minimal for caffeine and s-warfarin (mean AUC ratios 0.82-1.25). Maximum change in exposure for these substrates occurred 3-4 days after step-up dosing in cycle 1. These results suggest that after cycle 1, drug interaction from IL-6 effect has no meaningful impact on CYP activities, with minimal or moderate impact on CYP substrates. The highest risk of drug interaction is expected to occur during step-up dosing up to 7 days after the first treatment dose (1.5 mg/kg subcutaneously) and during and after CRS.
(© 2024 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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