Serum and Saliva Theophylline Levels in Adult Outpatients with Asthma and Chronic Obstructive Pulmonary Disease (COPD): A Cross-Sectional Study

Abstract

Due to a narrow therapeutic range, measurment of theophylline serum levels is highly recommended in patients with a long-term theophylline therapy. In this regard, since blood sampling is an invasive method, exploring alternative methods using other biological fluids in particular saliva samples are targeted. This study was designed to determine any relationship between serum and saliva levels of theophylline in patients with asthma and COPD, whom have been under xanthine–therapy for an extended period of time. Also, any relationship between serum or saliva levels of theophylline with possible explanatory factors was investigated. Adult (≥18 years) outpatients with a history of theophylline use (for at least 1 month) entered this study. Serum and stimulated saliva samples obtained 1 h before the morning dose and were measured using a high performance liquid chromatography (HPLC) method. To stimulate saliva production, patients chewed a piece of parafilm for 5 min before sampling. Relevant demographic information, medical and medication histories of the patients were also recorded. Collected data were entered into the SPSS (Statistical Package for Social Scientists, version 11.5) software and analyzed using the appropriate statistical tests (p<0.05). Eighty-six patients (44 males and 42 females) with a mean ± SD age of 58.72 ±14.23 years enrolled in the study. Mean±SD of serum and saliva concentrations of theophylline were 5.4±2.8 mcg/ml and 4.0±2.1 mcg/ml, respectively. Forty five patients (52.3%) had subtherapeutic serum levels of less than 5 mcg/ml. There was a significant direct relationship between serum and saliva levels of theophylline (p=0.0001, r = 0.91). Multivariate analysis led to a model in which only total daily dose of theophylline (mg) could remain as a predictor associated with the serum (p = 0.0002, r = 0.53) and saliva levels (p = 0.0001, r =0.47). A considerable association observed between serum and saliva levels of theophylline, confirms previous reports. The observed high frequency of the patients with subtherapeutic serum levels emphasizes the importance of implementing therapeutic drug monitoring (TDM) of theophylline in patients with a long-term theophylline therapy, using non-invasive alternative sampling methods e.g. saliva sampling.