Prediction of Optimal Time of Day for Salmeterol Based on Circadian Phases of Target Proteins in the Target Tissues

Abstract

Circadian rhythms are conserved across a wide range of organisms, including cyanobacteria, fungi, insects, and mammals. Approximately 50% of gene transcription, 8-38% of protein translation, and 13-22% of metabolites in mice have been shown to cycle with 24-hour rhythmicity. Approximately 75% of the current medications on the market target circadian-controlled pathways. However, current drug discovery and improvement studies are far from investigating the effect of time of day. In the current study, the optimal time of day for treating Chronic Obstructive Pulmonary Disease (COPD) with salmeterol is shown based on the circadian profiles of the target proteins in the target tissues. This calculation strategy aims to provide timing guidance for the drugs targeting rhythmic pathways or being metabolised by them. The current study also reveals different predicted optimal times of day for male and female mice, highlighting the importance of gender variability in circadian studies. The approach proposed in this research could be beneficial in studies that consider the circadian timing of medications.