Steady-state pharmacokinetics of a once-daily theophylline formulation (Euphylong) when given twice daily

In a multiple-dose crossover study in 18 healthy male volunteers the steady-state pharmacokinetics of Euphylong, which has been designed for once-daily evening administration, was investigated after conventional twice-daily administration. Under both modes of administration 2 plasma level profiles over 24-hours each were taken during steady-state (day 5/6 and day 8/9, respectively), in order to assess the reproducibility from day to day. The extent of absorption (AUC) was equivalent for both dosing schemes. The intentional differences in pharmacokinetic profiles between the once-daily and twice-daily administration were reflected in the maximum concentrations (15.0 vs 12.1 mg/l), the plateau time T75% Cmax (11.5 vs 17.1 hours), the percent peak-trough fluctuation (94 vs 47%) and the nocturnal excess (37 vs 4%). Results are given for day 8/9, but were practically identical on day 5/6. Thus, the twice-daily administration provides very smooth plasma levels over 24 hours, however, at the expense of the loss of the nocturnal excess which is of clinical relevance in the treatment of nocturnal asthma.