Navigating through chemometrics: Unveiling antibiotic-food interactions for improved pediatric formulations ahead.

Abstract

Background: Given the challenges of pediatric antibacterial therapy, it is crucial to formulate antibiotics with a lower potential for interaction with dietary interventions and tailor them for optimal administration in children. Chemometric methods allow us to analyze multiple interrelated variables simultaneously and uncover correlations.

Aim: We applied a chemometric approach to examine how food, beverages, antacids, and mineral supplements affect antibiotic bioavailability in adults and children, aiming to explore relationships between antibiotic structure, physicochemical properties, and post-meal changes in pharmacokinetic (PK) parameters.

Methods: We selected 95 antibacterial drugs for analysis, including beta-lactams (32), quinolones (25), macrolides (13), tetracyclines (16), and others (9). The input dataset comprised information from published clinical trials, chemical records, and calculations. We constructed hierarchical partial least squares (PLS) models with changes in PK parameters (ΔAUC, ΔC_max, ΔT_max, and Δ t ½) as response parameters and nine groups of molecular descriptors (M1-M9) as predictor parameters. We performed analyses separately in children and adults for different dietary interventions.

Results: In the final 10 PLS models, significant components explained 61-90% and 10.3-54.4% of the variance in the predictor and response parameter sets, respectively. We obtained 59 significant positive and negative correlations between antibiotic structure or physicochemical properties (molecular descriptors) and action in the human body in the presence of food, antacids, or mineral supplements (changes in PK parameters), of which 41 concern pediatric patients.

Conclusions: Chemometric methods can be helpful and valuable in investigating the interactions between antibiotics and dietary interventions. Using chemometrics may pave the way for formulating antibiotics for children with a lower potential to interact with food.