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Toxicity of a hepatotoxic laxative preparation in tissue culture and excretion in bile in man
Author(s) -
Dujovne C. A.,
Shoeman D.W.
Publication year - 1972
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1972134602
Subject(s) - laxative , lactate dehydrogenase , toxicity , cytotoxicity , pharmacology , cytotoxic t cell , neutral red , drug , chemistry , liver cell , medicine , biochemistry , enzyme , in vitro , constipation
Dioctyl sodium sulfosuccinate (DSS), 100 or 200 mg., was given orally to patients with indwelling T‐tube biliary drainage. Concentrations of the drug in bile measured by gas chromatography ranged from 4 to 9 × 10 −5 M. Before recent modifications, DSS and oxyphenisatin were the components of a laxative preparation, Dialose Plus. The cytotoxic potential of both drugs on human liver cell cultures (Chang) was quantitated by loss of lactate dehydrogenase and ß‐glucuronidase into surrounding tissue culture media after exposure to concentrations of the drugs between 10 −6 M and 2 × 10 −4 M for 4 to 24 hours. At 4 hours and higher concentrations, only DSS or the 2 drugs together were cytotoxic; at 24 hours high concentrations of oxyphenisatin became cytotoxic. At most other lower concentrations the addition of the 2 drugs to the same cultures resulted in greater cytotoxicity than either did separately. These data suggest that clinical hepatotoxicity might be facilitated when patients achieve “critical” concentrations of one or both of these drugs in liver parenchyma.