Effect of Febrile State on Theophylline Clearance in Asthmatic Acute Phase in Japanese Pediatric Patients

Abstract

The effect of a febrile state on theophylline clearance in the asthmatic acute phase was quantitatively investigated in 71 Japanese pediatric patients (42 males and 29 females) aged 2-< 7 years old. Theophylline clearance from each patient was estimated from the plasma steady-state theophylline concentration, which was retrospectively collected during constant-rate infusion of aminophylline. Theophylline clearances were grouped by the presence of a febrile state, and then these were compared in the same gender groups. In male pediatric patients, theophylline clearance during the febrile state was approximately 71％ (P < 0.001) of that during the afebrile state in the asthmatic acute phase. Similarly, in female pediatric patients, it was 85％ (P < 0.05) of that during the afebrile state in the asthmatic acute phase. Our findings suggest that the dose of theophylline in Japanese infants should be reduced during a febrile state in the asthmatic acute phase. However, we found some patients whose theophylline clearance in the asthmatic acute phase with fever was more than 50％ lower compared with the theophylline clearance in the asthmatic assumed-remission phase without fever. Therefore, as for the degree of dose reduction during a febrile state from the asthmatic remission phase, the effects of both febrile state and asthmatic acute phase should be simultaneously considered. We propose that the initial dose of theophylline during a febrile state in the asthmatic acute phase should be reduced by half of the dose in the asthmatic remission phase without fever, similarly to the recommendation of the American Academy of Pediatrics.