Title: PHARMACOKINETICS AND CLINICAL OUTCOMES OF TOBRAMYCIN IN ADULT CYSTIC FIBROSIS PATIENTS WITH ACUTE PULMONARY EXACERBATION

Running title: ASSESSING TOBRAMYCIN IN CYSTIC FIBROSIS

Authors: Daniel J.G. Thirion, PharmD^1,2, Kevin Koloskoff, PharmD^1,3, Jean-Alexandre Caissy, BSc^1,3, Elias Matouk, MD⁴, Amélie Marsot, PhD^1,3

Affiliations: ¹Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada; ²Pharmacy Department, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada; ³Laboratoire STP2, Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada;⁴Adult Cystic Fibrosis Clinic, Montreal Chest Institute, McGill University, Montreal, Quebec, Canada

Corresponding author:

Amelie Marsot: Faculty of Pharmacy, Université de Montréal, PO Box 6128, succ. Centre-ville, Montreal, Quebec, Canada H3C 3J7

E-mail: amelie.marsot@umontreal.ca

Telephone: 1-514-343-6111 ext. 5207

Fax: 1-514-343-6120

The data of this manuscript was presented as an abstract at the North American Cystic Fibrosis Conference, Oct 21-23, 2020, online.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors declare no conflicts of interest.

Key points:

The evaluation of regimens through their predictive attainment of PK/PD targets remains the fastest way to evaluate a dosing strategy and its factors.

Clinically history of APEs is predictive of clinical outcomes.

CF-specific variability is likely to cause the current tobramycin dosing regimen to be sub-optimal, rigorous identification of additional factors is needed to account for this variability.