Comparison of clinical effects and pharmacokinetics of once daily uniphyl and twice-daily theo-dur in asthmatic patients

Abstract

A pharmacokinetic study using theophylline syrup in adult asthmatic patients demonstrated a mean apparent volume of distribution of 0.38 liters/kg, mean elimination rate constant of 0.10 hours −1, and variable rates of clearance of theophylline (total body clearance of 0.38 to 0.96 ml/kg per minute). Subsequently, the asthmatic patients were compared using a cross-over design after maintenance Uniphyl (once daily at 8 a.m. or at 8 p.m.) and Theo-Dur (twice daily at 8 A.M. and 8 P.M.). Total daily maintenance theophylline dosage, calculated from the pharmacokinetic data, was identical in all three cross-over phases. At the end of each phase, plasma theophylline levels were measured every two hours and spirometric determinations were made every four hours (excluding 4 A.M.) for 24 hours. The following results were observed: (1) highest peak and mean plasma theophylline concentration and area under the concentration-time curves with evening Uniphyl (p < 0.05); (2) prolonged time-to-peak theophylline concentration after nocturnal compared with daytime dosing; (3) diurnal variation in pulmonary function and plasma theophylline concentrations; (4) no significant differences between the three maintenance treatments in asthmatic symptoms or spirometric results.