Influence of the combined chemotherapeutic drug tuboprim on drug metabolism.

Tuboprim (Pharmachim, Bulgaria) is a combined synergistic chemotherapeutic drug, containing rifampicin (Tubocin-Pharmachim) (TB) and trimetoprim (TM). In experiments on rats and mice the influence of single and repeated (4 days) doses of Tuboprim and of the corresponding doses of TB and TM on some drug metabolizing enzyme systems and other factors of drug metabolism was studied. The following indices were investigated: hexobarbital sleeping time (HBST), activities of hexobarbital oxidaze (HBO), aniline hydroxylase (AH), ethylmorphine-N-demethylase (EMND), uridindiphosphoglucuronyl-transferase (UDPGT), NADPH-cytochrome-C reductase and the cytochrome P-450, cytochrome b5 and microsomal protein contents. A single dose of TB (100 mg/kg in rats and 80 mg/kg in mice) inhibited HBO, EMND and AH; TM (30 mg/kg in rats and 20 mg/kg in mice) inhibited HBO and EMND, whereas Tuboprim inhibited EMND only. Repeated (4 days) treatment with TB provoked an induction of HBO, AH, and EMND accompanied by an increase of NADPH-Cyt-C reductase and cytochrome P-450, hem and microsomal protein content. Trimetoprim stimulated EMND only. The combined drug Tuboprim also produced an enzyme induction, but to a considerably less degree than did TB alone. UDPGT activity was not significantly changed.