Therapeutic index of taurocholate or tauroursodeoxycholate in experimental drug-induced cholestasis.
The therapeutic index of either taurocholate (TC) or tauroursodeoxycholate (TUDC) administration in the treatment of drug-induced cholestasis was evaluated in perfused rat liver using a dose-response study. During estradiol-17-beta-glucuronide cholestasis, TC was more effective than TUDC in ameliorating bile flow but showed a low margin of safety since high doses caused additional toxicity. In contrast, TUDC ameliorated cholestasis even at very high doses with no adverse effects. In the model of chlorpromazine cholestasis, TC infusion did not correct but rather aggravated cholestasis, whereas TUDC at nonsaturating doses reversed the cholestasis and only at very high doses caused some toxicity. TUDC shows a good therapeutic index and may be employed with a reasonable margin of safety in the treatment of drug cholestasis.
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Istituto Terapia Medica, II Università di Napoli, Italy.
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D000818:Animals; D002746:Chlorpromazine; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy*; D004958:Estradiol / Q000031:analogs & derivatives; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage*; D013656:Taurocholic Acid / Q000008:administration & dosage*
D002756:Cholagogues and Choleretics; C025483:estradiol-17 beta-glucuronide; D004958:Estradiol; D013655:Taurochenodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine; D002746:Chlorpromazine