Nassar, Yomna M. http://orcid.org/0000-0003-0507-7130
Hohmann, Nicolas
Michelet, Robin http://orcid.org/0000-0002-5485-607X
Gottwalt, Katharina
Meid, Andreas D.
Burhenne, Jürgen
Huisinga, Wilhelm http://orcid.org/0000-0002-5249-3914
Haefeli, Walter E. http://orcid.org/0000-0003-0672-6876
Mikus, Gerd http://orcid.org/0000-0003-1783-133X
Kloft, Charlotte
Funding for this research was provided by:
Department of Clinical Pharmacology and Pharmacoepidemiology at Heidelberg University Hospital and the Department of Clinical Pharmacy and Biochemistry at the Freie Universitaet Berlin
Freie Universität Berlin
Article History
Accepted: 21 August 2022
First Online: 4 October 2022
Declarations
:
: Open Access funding enabled and organized by Projekt DEAL. This trial and data analysis were funded by internal resources of the Department of Clinical Pharmacology and Pharmacoepidemiology at Heidelberg University Hospital and the Department of Clinical Pharmacy and Biochemistry at the Freie Universitaet Berlin. No medical writing support was used.
: Yomna M. Nassar, Nicolas Hohmann, Katharina Gottwald, Robin Michelet, Andreas D. Meid, Jürgen Burhenne, Walter E. Haefeli, and Gerd Mikus declare that they have no conflicts of interest that might be relevant to the content of this article. Charlotte Kloft and Wilhelm Huisinga report grants from an industry consortium (AbbVie Deutschland GmbH & Co. KG, AstraZeneca, Boehringer Ingelheim Pharma GmbH & Co.KG, Grünenthal GmbH, F. Hoffmann-La Roche Ltd., Merck KGaA, and Sanofi) for the PharMetrX PhD program. Charlotte Kloft reports a grant from the European Commission for Innovative Medicines Initiative-Joint Undertaking (‘DDMoRe’).
: All procedures performed in studies involving human participants were in accordance with Good Clinical Practice (ICH-GCP) guidelines and the ethical standards of the current Declaration of Helsinki. The trial protocol (EudraCT 2013-004869-14) was approved by the responsible Ethics Committee of the Medical Faculty of Heidelberg University and the competent authority (BfArM, Bonn, Germany).
: All included volunteers gave their written informed consent prior to any study procedures.
: Not applicable.
: The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
: The NONMEM model code is available in the ESM.
: NH, KG, WEH, and GM designed the clinical study conception and conducted the study; JB performed the midazolam bioanalytical analysis; YMN and ADM conducted the data analyses; YMN, RM, GM, and CK thoroughly discussed the data analysis and were involved in the interpretation of results; RM, WH, and CK provided methodological support; WH, GM, and CK provided supervision; the first version of the manuscript was drafted by YMN; all authors critically reviewed, edited, and commented on previous versions of the manuscript, and approved the final version of the manuscript.