Variations in theophylline concentrations detected by 24-hour saliva concentration profiles in ambulatory children with asthma

Abstract

Sustained-release theophylline (SRT) therapy was monitored in ambulatory children with asthma by measuring theophylline in citric acid-stimulated saliva. Ninety-six around-the-clock saliva theophylline profiles were performed in 59 children (median age, 8.3 years) under routine life conditions. Five to seven stimulated saliva samples were collected by parents at home during a 24-hour period. Highest (Cmax) and lowest (Cmin) saliva theophylline concentrations (Sal-TC) were not consistently found after or before medication, respectively. Cmax occurred during morning hours (before or after medication) in 82% of patients. Cmax was found immediately before morning or evening dose in as many as 25% of patients. Cmin occurred in 70% of children during evening hours. Cmin was found 4 hours after morning or evening dose in 19% of patients. Excessive fluctuation in Sal-TC between pre- and post-SRT doses during both day and night hours occurred in six patients (286% +/- 87% (mean +/- SD)). Marked circadian variation in Sal-TC was disclosed in 23% of children. The first profile performed was therapeutically satisfactory in only 39% of patients; satisfactory profiles were achieved in other children after changing daily SRT dose or dosing interval. Determination of theophylline concentration in stimulated saliva specimens obtained frequently during a 24-hour period and under routine life conditions is practical and extremely valuable for close monitoring and individualization of theophylline therapy in ambulatory children with asthma.