The kinetic interaction of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and theophylline has been studied in vitro (displacement from protein binding) and in vivo in healthy male non-smokers after oral administration. In a randomized, three-way cross-over study, 12 subjects received at weekly intervals either separated or combined single doses of picumast dihydrochloride (10 mg) and theophylline (7 mg/kg b.w.) Picumast and its metabolites were analysed in plasma and urine up to 24 h and theophylline was assayed in plasma during the same time. Theophylline pharmacokinetic parameters like time to peak concentration, peak concentration, elimination half-life, area under the plasma concentration-time curve and oral clearance were not changed after a concomitant dose of picumast dihydrochloride. The combination of theophylline and picumast dihydrochloride revealed no significant changes in the picumast pharmacokinetic parameters t1/2, tmax and CLR. However, Cmax and AUC0-24 decreased significantly by 11% and 7%, resp. Additional theophylline administration significantly increased peak concentration of the intermediate active metabolite M2 by 23% from 7 to 8.6 ng/ml. The absorptive parameters, i.e. time to peak and peak concentration of M1 as well as the AUC calculated from 0-24 h and the renal clearance did not differ in single or combined picumast dihydrochloride administration. A supplementary in vitro study showed no change in plasma protein binding of picumast (100 ng/ml) in the presence of theophylline (20 micrograms/ml) and vice versa. In all volunteers picumast dihydrochloride proved to be safe and well tolerated and treatment was not negatively influenced by theophylline co-administration.(ABSTRACT TRUNCATED AT 250 WORDS)