Effect of chlorpromazine and erythromycin on bile salt-induced cholestasis in the rat

The effects of subacute administration of chlorpromazine HCI (CPZ), erythromycine base and erythromycin estolate on the cholestatic response to intravenous taurolithocholate (TLC) and taurochenodeoxycholate (TCDC) in the rat were investigated. All three enhanced the recovery of bile flow after TCDC but not after TLC. Erythromycin base and estolate enhanced bile flow recovery after TCDC and potentiated the increase of plasma 5'-nucleotidase, as did CPZ. Neither erythromycin estolate nor CPZ precipitated a cholestatic response in rat maintained for 9-13 days on a diet supplemented with 0.05% lithocholic acid. It is concluded that the interaction of CPZ and erythromycins with bile salts is not based on the cholestatic properties of the drugs, and hence is not a practical way of distinguishing cholestatic from non-cholestatic drugs.