Development and Evaluation of a Height-Based Tobramycin Initial Dosing Nomogram for the Treatment of Adult Cystic Fibrosis Pulmonary Exacerbations

Abstract

Tobramycin is widely used to treat pulmonary exacerbations of cystic fibrosis. Height has been previously found to be significantly more predictive of tobramycin pharmacokinetics than body weight. This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing. Monte Carlo simulations were performed to develop a nomogram representing the doses required to reach Cmax targets at different heights. Cmax data observed at 2 clinical centers [McGill University Health Centre (MUHC) and Institut universitaire de cardiologie et pneumologie de Québec (IUCPQ-UL)] were compared with population-predicted Cmax using the doses derived from the nomogram alongside a fixed dose. Height-based dosing resulted in significantly less variable-predicted Cmax values [coefficient of variation (CV) MUHC = 15.7% and IUCPQ-UL = 10.8%] than the Cmax values observed in clinical practice (CV MUHC = 30.0% and CV IUCPQ-UL = 26.9%) and predicted Cmax values obtained from a fixed dose (CV MUHC = 21.2% and CV IUCPQ-UL = 16.3%). An initial dosing nomogram was developed to help reduce pharmacokinetic variability in the observed Cmax. More precise dosing would allow for better clinical outcomes in adult patients with cystic fibrosis.