[Experiences with the rectal use of chemotherapeutic agents. 2. Pharmacokinetic examinations with animals]

The aim of the investigations was to optimise vehicle for trimethoprim (TMP) suppositories ready for clinical trials. The rectal absorption of TMP was studied in anaesthetized rats. The drug liberation properties of the five mixed vehicles with promising in vitro results (Part 1.) were studied. The course of the blood level curves was monitored with serial sampling. The TMP concentration of blood was determined by bioassay. Individual bases were compared with the use of the pharmacokinetic parameters derived from the analysis of the obtained blood level curves, with special respect to biological availability (BA). The extent of bioavailability is influenced considerably by the hydro-, lipo- or lipohydrophilic property of the vehicle. TMP, if incorporated in the proper vehicle, is absorbed well. With three vehicles the extent of absorption exceeded the absorption seen with oral administration on the same model (BA = 38.8%). The best results were achieved with the lipophilic base Witepsol W 35 containing 10% of Polysorbate 20 and 10% of Polysorbate 61 (BA = 63.8%) and with Witepsol W 35 containing 10% of Polysorbate 60 (BA = 64.9%). The hydrophilic Macrogol 1540 vehicle containing 5% of Macrogol 400 had only slightly worse results (BA = 52.9%). In the case of the lipohydrophilic Witepsol W 35 vehicle with 10% of Polysorbate 20 and 10% of Polysorbate 61 content a significant negative exponential relation was found between the administered doses and their respective bioavailability values, this tendency had been observed during the in vitro examinations, too. No such relation was found in the case of the lipophilic Witepsol W 35 vehicle containing 10% of Miglyol 812.