sf-837 and Chemical-and-Drug-Induced-Liver-Injury

In rats, troleandomycin induces microsomal enzymes and promotes its own transformation into a metabolite forming an inactive complex with the iron (II) of cytochrome P-450; eventually, several monooxygenase activities are markedly reduced. In humans, troleandomycin also induces microsomal enzymes, and forms an inactive cytochrome P-450-troleandomycin metabolite complex; the clearance of antipyrine, that of theophylline, and that of methylprednisolone are markedly reduced. The concomitant administration of troleandomycin and other drugs may produce ischaemic accidents (ergotamine), cholestasis (oral contraceptives) and neurologic signs of intoxication (theophylline or carbamazepine). Qualitatively similar effects are produced, in rats and in humans, by erythromycin. These effects, however, are much weaker than those of troleandomycin. In humans, the clearance of antipyrine and that of theophylline are only slightly affected. Drug interactions have been reported in a few patients only. Josamycin and midecamycin do not form cytochrome P-450-metabolite complexes in rats. In humans, these macrolides do not inhibit the clearance of theophylline; midecamycin does not inhibit the clearance of antipyrine. Although a case of possible josamycin-ergotamine interaction has been reported, the role of josamycin may be questioned in this isolated instance. Midecamycin, or josamycin, might be preferred to other macrolides in those patients who must receive other drugs metabolized by cytochrome P-450.

Topics: Amines; Animals; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Enzyme Induction; Erythromycin; Humans; Leucomycins; Oxidation-Reduction; Pharmaceutical Preparations; Rats; Species Specificity; Troleandomycin

We report here the first case of symptomatic acute hepatic injury due to midecamycin in a 58-year-old man. The clinical picture was compatible with a hypersensitivity syndrome with cutaneous, renal and hepatic involvement. Liver eosinophil polynuclear infiltrate, hypereosinophilia and acute interstitial nephritis were consistent with the hypothesis of an immunoallergic mechanism.

Topics: Acute Disease; Biopsy; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Humans; Leucomycins; Liver Function Tests; Macrolides; Male; Middle Aged

Hepatotoxicity by macrolide antibiotics, particularly erythromycin and derivatives, is a side effect extensively described in the literature. Midecamycin is a semi-synthetic derivative of this family with a wide safety margin of which isolated references of possible secondary hepatobiliary effects have been referred. The present clinical observation describes a case of cholestatic hepatitis which, in our opinion, was related to the administration of diacetyl midecamycin which evolved favorably following discontinuation of the drug. Despite its exceptional frequency and based on the wide therapeutic diffusion of this group of antibiotics, we believe this case to be of interest.

Topics: Aged; Aged, 80 and over; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis; Clinical Enzyme Tests; Female; Hepatitis; Humans; Leucomycins; Liver; Macrolides