This study was based on a sample from the 2020 National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), taking 1% of these patients with a clear ID number (the ID number was used to obtain information of the patient's prescription) and ensuring that the patients were balanced in terms of gender.
A total of 3973 patients were enrolled in the study and analyzed for data on gender, dosage forms, and concomitant medication by five years age group. Among the 1148 patients who had confirmed theophylline prescriptions, only 13 had ever been monitored for TDM. And, as shown in Figure 1, the most commonly administered dosage form was not 400 mg/day as a usual rule (<30.8% 200="" of="" but="" rather="" day="">53.8% of patients).
Figure 1, Daily dose of theophylline in therapeutic drug monitoring and unknown group
In the association analysis of theophylline and concurrent drugs in a cohort of elderly patients over the age of 80 years, 174,172 prescriptions were studied, and 1,476 prescriptions for theophylline. Of these, fluvoxamine was reported to have the most increase in theophylline exposure (AUCR=2.38), and it was confirmed that theophylline was used concurrently in 0.31% of the patients. Among patients taking allopurinol, 2.60% were taking theophylline concurrently, and theophylline had the highest lift value of 3.03 among the precipitant drugs examined in the association analysis. 0.0687% of patients were using famotidine and theophylline concurrently, which had the highest supportive value of the precipitating drugs examined as shown in table 1.
Table 1 Association analysis of drugs influencing theophylline exposure (over 80 years old)
Plasma concentrations of theophylline were analyzed in three age groups: 30, 65, and 80 years of age, in people who took fluvoxamine, or allopurinol, or famotidine at the same time as theophylline. The results showed that theophylline trough concentrations and AUCR were 1.82-fold and 1.65-fold higher, respectively, in 80-year-old patients, and 1.50-fold and 1.39-fold higher, respectively, in 65-year-old patients, compared with 30-year- young patients. The trough concentration and AUCR were 1.35 times higher in female than in male. As shown in Figure 2.
Figure 2 Simulated plasma theophylline concentration–time profile in 30-, 65-, and 80-years patients. Red, AUCR = 2.38 (fluvoxamine); orange, 1.56 (famotidine); green, 1.34 (allopurinol); and blue, 1. AUCR: area under the concentration–time curve ratio. Shaded region: target range (5–20 µg/mL).