THERAPEUTIC INDEX OF TAUROCHOLATE OR TAUROURSODEOXYCHOLATE IN EXPERIMENTAL DRUG-INDUCED CHOLESTASIS

The therapeutic index of either taurocholate (TC) or tauroursodeoxycho late (TUDC) administration in the treatment of drug-induced cholestasi s was evaluated in perfused rat liver using a dose-response study. Dur ing estradiol-17-beta-glucuronide cholestasis, TC was more effective t han TUDC in ameliorating bile flow but showed a low margin of safety s ince high doses caused additional toxicity. In contrast, TUDC ameliora ted cholestasis even at very high doses with no adverse effects. In th e model of chlorpromazine cholestasis, TC infusion did not correct but rather aggravated cholestasis, whereas TUDC at nonsaturating doses re versed the cholestasis and only at very high doses caused some toxicit y. TUDC shows a good therapeutic index and may be employed with a reas onable margin of safety in the treatment of drug cholestasis.