Revealing of pharmacokinetic peculiarities of surface active drug promethazine in its interaction with caffeine in rabbits

► A significant increase of bioavailability of promethazine is observed under the influence of caffeine. ► The character of changes in the first-pass effect of caffeine under the influence of promethazine is depended on the sequence of administration of drugs. ► We proposed formation of certain complexes of caffeine with surface active molecule of promethazine.