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

The interaction of caffeine and promethazine in rabbits has been investigated. The drugs were administered as single oral doses (200 mg caffeine and 100 mg promethazine) as well as simultaneously with an interval of 15 min. The sequence of administration of the drugs was varied. fluence of caffeine on the pharmacokinetics of promethazine is expressed by: (a) strong increase of Cmax, AUC, AUMC and MRT of promethazine; (b) decreasing of kel, CL and Vss of promethazine. Significant changes are also observed in the pharmacokinetics of caffeine under the influence of promethazine. Besides these changes are depending on the sequence of administration of drugs. The values of Cmax, AUC, AUMC and MRT are reduced, but values of kel, CL and Vss occur when promethazine enters first and then caffeine. In contrast to this, the values of Cmax, AUC and AUMC increase, CL and Vss decrease, but values of MRT and kel remain practically unchanged in case when caffeine was administered first and then promethazine. ontrivial interaction of drugs may be stipulated by formation of sufficiently stable complexes of promethazine and caffeine in small intestine. It is probable that the structure and properties of these complexes are different in various mixtures and are depending on the sequence of administration of drugs. The presystem elimination of caffeine is enhanced, but first-pass effect of promethazine is suppressed in complex when promethazine enters first. The first-pass effect in complex is suppressed for both drugs when caffeine is administered first and then promethazine.