[Fulminant liver failure in tuberculostatic therapy. A contribution to clinical aspects and pharmacokinetics].
A 23-year old female patient on a prolonged regimen of tuberculostatic chemotherapy finally developed fulminant hepatic failure shortly after addition of hormonal contraception. The pathophysiology of this almost fatal drug reaction is described as a pharmacokinetic interaction: the inherent hepatotoxicity of prothionamide-the drug finally prescribed during convalescence-was significantly potentiated by the Cyt-P-450-inducing effect of the progestagen component of the hormonal contraceptive. Potentiation of hepatotoxicity in connection with tuberculostatic regimes containing rifampicin is well known and this pharmacokinetic phenomenon also pertains to the combination with other Cyt-P-450-inducing drugs such as, for instance, anticonvulsants. However, since the maximum of rifampicin-related Cyt-P-450-inducing effect is limited to the initial 2-3 weeks of therapy, the hepatotoxic risk triggered by this rifampicin-related induction may decline during continuation of therapy. This, unfortunately, does not pertain to the other Cyt-P-450-inducers, whose inductive effect is not time-limited. Progressive severe hepatic damage may follow from such interaction as demonstrated in this case report.
Medizinische Klinik der Rheinischen Friedrich-Wilhelms-Universität, Bonn.
E
E
Musch
W K
WK
Lelbach
R
R
Stiens
P
P
Bülau
O
O
Köster
D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006501:Hepatic Encephalopathy / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008234:Lynestrenol / Q000008:administration & dosage; D008656:Mestranol / Q000008:administration & dosage; D011515:Prothionamide / Q000009:adverse effects; D014396:Tuberculosis, Pleural / Q000188:drug therapy*
D000995:Antitubercular Agents; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D011515:Prothionamide; C002746:Noracycline; D003577:Cytochrome P-450 Enzyme System; D008656:Mestranol; D008234:Lynestrenol
Fulminantes Leberversagen unter tuberkulostatischer Therapie. Ein Beitrag zur Klinik und Pharmakokinetik.