AIM: This study evaluated the pharmacokinetic interaction between theophylline and antofloxacin in vivo and in vitro.METHODS: A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects.Oral medications were antofloxacin, theophylline,or theophylline plus antofloxacin.For antofloxacin, morning doses were 200 mg on day 2 to 5 and 400 mg on day 1.For theophylline, daily doses (twice a day) were 400 mg on day 2 to 4 and morning doses were 200 mg on day 1 and 5.Plasma and urinary pharmacokinetics of antofloxacin and theophylline were characterized after the first dose and last dose.The effect of antofloxacin on theophylline metabolism was also investigated in pooled human liver microsomes.